August 3-7, 2017; Indianapolis, IN; Full Report – Draft

This report features our full coverage from the American Association of Diabetes Educators 44th annual meeting (AADE 2017) held in Indianapolis, IN from August 3-7. Alongside ~3,000 attendees, we found ourselves incredibly impressed by the practical, real-world perspectives at this meeting. Yet again, AADE management and team outdid itself in creating a truly valuable meeting – the quality grows higher and higher each year and we were supremely impressed with the innovation demonstrated at this gathering.

Below, we have divided our coverage into five categories: (i) Themes; (ii) Diabetes Technology; (iii) Diabetes Therapy; (iv) Additional Topics; and (v) Exhibit Hall. 

This absolutely felt like a busier-than-usual meeting on the technology side, with a major focus on digital health and educators’ evolving role on the front lines. A standout keynote from BCG digital health expert Mr. Chris Bergstrom embodied the general message: We are in the middle of a revolution in the diabetes care, and it is up to those on the front lines of care delivery to play a pivotal role in testing products, providing feedback, and driving more connected, continuous care. We also picked up on a ton of dialogue about diabetes technology “in the wild” – once diabetes devices get into patients’ hands, experiences vary dramatically. Our own Adam Brown and Diabetes Mine’s Amy Tenderich highlighted how design intention, labeling, and real-world performance often differs from clinical trials and product labels. Social media is frequently touted as a source of peer support, but numerous speakers pointed to its potential as a source of real-world data on how patients are actually using devices in the real world – we saw the first Instagram analysis we’ve ever seen at a conference!

In diabetes therapy, we observed keen enthusiasm for the new class of basal insulin/GLP-1 agonist fixed-ratio combinations as well as for newer agents like GLP-1 agonists and SGLT-2 inhibitors as basal insulin intensification strategies, though these discussions were always contextualized against underlying concerns over the often prohibitively high cost of diabetes care.

Big picture, we heard about the need to move beyond A1c alone, a greater focus on prediabetes and prevention, a continued flurry of interest in the microbiome, and several fascinating talks on the psychology of diabetes – including how to manage comorbid diabetes and depression and importance of the language we use to discuss diabetes.

Themes

Diabetes Technology

Educators Must Prepare for the Rise of Digital Health – How Will Their Jobs Evolve?

• From Chris Bergstrom’s (BCG) fantastic, packed keynote on the state of digital health to AADE/WellDoc’s introduction of the “Diabetes Digital Health Learning Network,” there seemed to be a bigger emphasis on technology this year. In a stunning multimedia presentation, Mr. Bergstrom illustrated the power and potential of digital, and convincingly explained how we are truly in the midst of transformation in diabetes management – and therefore, the role of educators. Digital health funding has accelerated (even in the past year), tech-pharma partnerships abound (“some very strange bedfellows,” mused one Tweeter), and remote coaching is seeing more and more interest thanks to increasing device connectivity. Mr. Bergstrom really struck a chord with the audience, and we heard that attendance at some digital-oriented exhibit hall booths was up 10x after his talk! This was among the most buzzed about talks at AADE 17. Meanwhile, AADE/WellDoc’s Digital Health Learning Network was introduced at the conference, which aims to support educators as they leverage digital health in clinical care. The initiative seems like an effort to build the category of prescribed digital health apps (including WellDoc’s BlueStar) – can it help educators who are daunted by technology? It is great to see AADE take a stance to try to stay ahead of the digital curve, a trend we haven’t yet seen to the same degree at some other organizations (for example, EASD, whose annual meeting is upon us). Mr. Bergstrom, too, encouraged attendees to “take a leadership role to experiment with these digital health solutions, provide feedback to the patients who are using them and the people who are making them. Use them to reach more patients than you ever have. Basically, be superhuman.”
• A concern we noticed in many sessions: some educators questioned whether digital technology would eventually replace educators’ jobs. It’s difficult to know long term, though in the near term, many speakers argued technology will change and improve the role of educators, as we have argued over many years that it would. Adam Brown emphasized that connected devices, clinical decision support, and automation will analyze reams of diabetes data, freeing up educators to address the myriad other factors related to quality of life burden that is so important - mental health, behavior change, etc. As expected, coaching and remote education via telemedicine were big topics across the conference, as more diabetes education shifts beyond face-to-face interaction. In a separate session, highly regarded former AADE President Ms. Malinda Peeples (now with WellDoc) also noted that educators must focus on doing this from a population-level view, or the masses of patients who need help won’t be reached effectively. Bottom line: Digital health has potential to deliver more continuous care and insight far beyond current practices, but it must be designed carefully with the patient at the center AND to make life easier for providers. Educators, of course, can help ensure products meet this very high bar.

Devices “in the Wild” – What Are Patients Actually Doing?

• AADE was packed with sessions offering providers useful tips and tricks for navigating the rapidly expanding field of diabetes technology. Attendees were reminded that a lot more goes into optimizing technology than can be found in an instruction manual. Even before optimization, simply choosing a device is complicated, something our own Adam Brown and DiabetesMine’s Amy Tenderich noted in their completely packed session. (Download Adam’s slides here and Amy’s slides here.) We’re glad to see “usability” of devices increasingly highlighted at conferences – products need to fit into patients’ daily lives and are about far more than the “human factors” needed to secure approval. Small tweaks can have a big impact on device performance and glycemic outcomes, and managing patient expectations, whether for sensors or automated insulin delivery, was a major theme throughout the conference. IDC’s Ms. Shannon Beasley and Ms. Beth Olson discussed the importance of advising patients on the 670G to expect more than 3-4 calibrations per day and to see post-meal rises, even with hybrid closed loop running. In 670G users she’s observed, Ms. Beasley noted the substantial gains in mental relief that accompany 670G adoption. Still, the 670G is by no means a perfect system – Ms. Beasley acknowledged the lack of a sharing feature, though noted that there are “rumblings” sharing will return in a later iteration, and that some patients find the burden to be too much effort relative to the glycemic improvements.
  
  • An Instagram hashtag analysis performed by Dr. Michelle Litchman’s group showed that 64% of #Dexcom-tagged posts pictured alternate site wear not on the FDA-approved abdomen. Companies can learn from such real-world behavior! Alternative sites were: the back of the arm (39%), thigh (13%), the forearm, back, front of the arm (3% each), the calf (2%) (!), the buttocks (0.6%), and other (10%). We similarly noticed lots of CGMs worn on the upper arm at Friends for Life this year, and we wonder if the next-gen of sensors will pursue this wear location, including Dexcom’s G6 (FDA submission in September). Of course, Abbott’s FreeStyle Libre was the arm-wear trailblazer, in terms of approved products. 100% “on-label” use is rarely (probably never), a reality, so it’s crucial that providers, regulators, and companies understand why patients go off-label and what implications that has for positive real-world experiences. 
• Ms. Amy Tenderich pointed out that DIY automated insulin delivery devices (OpenAPS, Loop) have more and more users entering clinicians’ offices – educators need to understand what patients are actually doing so they can be better informed about what to ask. To this end, Ms. Dana Lewis of Open APS encouraged diabetes educators to take advantage of the open source community to learn more about how to best serve patients who are “Looping” (using DIY closed loop systems) – her talk shared a number of fascinating new OpenAPS developments, including “eating soon mode,” “autosensitivity,” and “autotune.” Adam also shared his experience wearing a DIY Loop system, cautioning educators to manage patient expectations (“YOU STILL HAVE TO BOLUS”), letting automated systems correct moderate highs, eating fewer correction carbs to correct lows, and planning for exercise ahead of time. Many providers understandably fear DIY devices (e.g., liability concerns), so it was great to see AADE giving patient innovators a platform to share their perspectives. People with diabetes are increasingly teaching each other and improving products on their own, changing the paradigm of education and hopefully influencing R&D priorities.

More Attention And Clamoring for Insulin Dose Titration + Smart Pens

• In the year since AADE 2016, the insulin dose titration and smart pen landscapes have seen more development momentum and clinical interest – a trend reflected at this year’s meeting. Dr. Bruce Bode got the ball rolling in a symposium on the first official day of AADE, speculating that Novo Nordisk, Sanofi, and Lilly are committed to sending dose information from their delivery devices to the cloud (ASAP), “hopefully by the end of 2018.” Novo Nordisk is working with their own disposable pens, Sanofi is working with pen caps like Common Sensing, and Lilly is working with pen cartridges with Companion Medical, he noted. Soon, it may not be enough to just supply a drug like insulin – companies will have to consider supplying services surrounding their drugs to capture real-world data, help with titration, and monitor populations. Dr. Bode added that Glytec is working with multiple companies to incorporate continuous glucose data into its FDA-cleared titration system – great to hear, since current systems only use BGM data, and in many cases, manually entered values. We look forward to seeing this early field move toward scale, reimbursement, and outcomes – insulin dose capture is a long time coming and stands to augment titration algorithms and general therapeutic decision making to help people better manage their diabetes. That said, smart pens and dose titration are not widespread products right now – what will the field look like by AADE 2017? Will it still be another few years until advances are widely available?
• Two of the first basal titration apps to receive FDA clearance – iSage Rx (Amalgam Rx) and Insulia (Voluntis) – made their first and second exhibit hall appearances, respectively. While neither of these products has rolled onto the market in a major way, it sounds like they’re both moving along, expanding indications and gaining some early traction. Two big health centers have signed on to use iSage Rx, while Voluntis’ US pilot programs are moving forward. In addition, Companion Medical reaffirmed its 2017 launch timing and startup DiabNext showed off its suite of diabetes products, including a connected pen attachment. All of these products have seen more momentum and news in the past year, and we wonder how long it will be before insulin injectors are automatically prescribed a titration app.

The Role of Glucose Monitoring in Type 2s Not On Insulin

• Following an ADA that provided mixed evidence for the efficacy of SMBG in non-insulin-treated type 2s, Dr. Laura Young (PI on the Monitor Trial) said that she has stopped recommending fingerstick testing for some of her patients. The other data presented at ADA – from the SMBG study – showed an A1c benefit in the group performing fingersticks. Theoretically, a lot can be learned from paired, more frequent, and structured monitoring (i.e. “If I eat tuna salad, this is what happens” or “If I go for a five-mile run, this is what happens”), but it needs to be intuitive and coupled with the right education on when to check and what the numbers mean. At this point, the evidence supporting SMBG in non-insulin type 2s remains controversial, but it’s an area we hope will change significantly once CGMs are low-cost, reimbursed, easy enough to use for a broad population, and coupled with education and behavior change programs. In the meantime, feedback from even intermittent CGM (blinded or unblinded) should hopefully have a bigger impact than infrequent SMBG (see Dr. Irl Hirsch’s compelling cost-effectiveness argument in favor of intermittent RT-CGM from ATTD). In an Abbott-sponsored symposium, Dr. Etie Moghissi raved about FreeStyle Libre Pro (“this has truly revolutionized the way we look at patients’ data retrospectively”), positive views we’ve heard at sevreal other conferences this year. Dr. Moghissi also brought up another area of debate – when should blinded vs. real-time intermittent CGM be used? She noted that real-time, intermittent CGM may alter behavior significantly, obscuring what happens on a “typical” day. Of course, the value of real-time CGM is that it offers in-the-moment patient learning in a way that blinded CGM cannot approach. We hope this can be addressed as more studies look at deploying CGM in type 2 diabetes.

Social Media as a Medium for Peer Support, but Also a Glance at Diabetes Sentiments and Real-World Product Use

• In addition to off-label behaviors (see above), social media might even provide a sentiment analysis – which aspects of someone’s diabetes care are going well or poorly? Mr. Chris Bergstrom showed some stunning visuals representing “big data” derived from comments on social media forums. This sort of “sentiment analysis” could rapidly alert manufacturers and educators (and FDA and payers!) to pain points that need to be addressed, as well as areas in which patients are satisfied. For example, seeing alternate site wear in 64% of cases could alert Dexcom to investigate these other sites, develop protocols and training materials around their use, and pursue an indication from FDA.
• We also heard from Lipscomb University’s Dr. Kevin Clauson, who identified social media as one of five key drivers of successful digital health development. However, we were surprised to see that only about a third of the audience (comprised largely of educators) in one session indicated familiarity with the diabetes online community. In one year, the average patient interacts with providers only 0.007% of the time. By visiting online communities, providers can help bridge this gap, gaining insight into the actual lives lived by those with diabetes. The online community can also help with troubleshooting and training from peers, knowledge educators can then bring into their own practices.  
• The first pre-conference event that we attended – one of our favorites – was the #DSMA (Diabetes Social Media Advocacy) Twitter chat, hosted by Ms. Cherise Shockley and Mr. Scott Johnson. We heard heartfelt insights on living with diabetes from an all-star panel of patient advocates, joined by members of the diabetes online community Tweeting in. This is such a valuable resource for all people with diabetes, especially those who are feeling isolated. Beyond Type 1’s Ms. Mila Ferrer talked about how the only way she could “survive” with her young son who has type 1 diabetes was to sign into the Children with Diabetes chatroom at 8 pm, when another mom with an 18-year-old son tended to be available – this is where she obtained the answers to critical questions, and she couldn’t have imagined raising a child with type 1 without this amazing resource.

Diabetes Therapy

CANVAS Commentary Galore: Amputations and Risk Mitigation

• In the wake of full CANVAS results presented at ADA 2017, commentary on this CVOT and the complicated risk/benefit profile of J&J’s SGLT-2 inhibitor Invokana (canagliflozin) were, understandably, a big part of the conversation on what new insights diabetes educators should know. With this trial, Invokana became the second SGLT-2 inhibitor on the market with demonstrated CV efficacy (following Lilly/BI’s empagliflozin, branded Jardiance). CANVAS builds a compelling case for an SGLT-2 cardioprotective class effect. In contrast to the exciting 14% risk reduction for three-point MACE (non-fatal MI, non-fatal stroke, CV death), however, was the nearly two-fold risk for lower limb amputations associated with canagliflozin vs. placebo. Real-world diabetes care providers want to know what to make of this – and indeed, we were pleased to note so much curiosity about Invokana, amputations, and the SGLT-2 class as a whole from educators at this conference. The topic even came up at sessions entirely unrelated: In a session on combination therapy, Ohio State’s Dr. Kittie Wyne made the astute point that many people with amputations in CANVAS has baseline peripheral vascular disease (PVD), and she called for a dedicated clinical study of patients with diabetes/PVD. In a talk on CV risk management, Dr. Anthony McCall went a bit further, recommending empagliflozin over canagliflozin for patients with PVD. In a Janssen-sponsored product theater, Dr. Eden Miller emphasized that amputation risk is very low in the real world even for a diabetes patient population. She advocated that this risk can be well-managed with diligent monitoring – a sentiment echoed by many thought leaders soon after the safety outcomes data read out at ADA, with some even presenting this as an opportunity to enhance patient education around foot care in diabetes (a topic too-often overlooked). Dr. Miller remarked, “every time my patients come in, shoes are off.” We hope the AADE 2018 agenda might even feature symposia centered around best practice strategies for foot care.
• There seemed to be near-consensus from AADE speakers that CANVAS data should not sway everyone away from Invokana toward Jardiance (or away from all SGLT-2 agents), but rather, that proper patient selection and proactive foot care with Invokana are paramount going forward. Said Dr. Wyne, “if someone’s doing well, and is stable on any therapy, I wouldn’t recommend changing it.” Instead, she identified PVD as a key risk factor to look out for (among other risk factors, like prior amputation). Enhanced education around foot care will be key, and part of this includes regular monitoring of the feet for people with diabetes. As Janssen’s VP of Medical Affairs for Cardiovascular and Metabolism Dr. Robert Cuddhiy pointed out, amputations in the CANVAS trial were usually preceded by an infection or some other warning sign, one that could presumably be caught so that an amputation is avoided. Dr. James List, Global Therapeutic Head of Cardiovascular and Metabolism at Janssen, suggested that this safety finding could kick-start a movement toward better patient education on foot care. We’d love for J&J to be a leader in this initiative. 

Concerted Education on New Class of Basal Insulin/GLP-1 Fixed Ratio Products

• While basal insulin/GLP-1 agonist fixed-ratio combinations were perhaps the most highly-anticipated new diabetes drugs in recent history, commercial uptake of Sanofi’s Soliqua (insulin glargine/lixisenatide) and Novo Nordisk’s Xultophy (insulin degludec/liraglutide) has lagged behind clinical enthusiasm – to this end, we loved the emphasis on these advanced therapies to a diverse audience of diabetes educators at AADE 2017. Without a doubt, it’s disheartening to see a product that Dr. John Buse endorses as the “most effective anti-hyperglycemic agent on the planet” dispensed at relatively low volume in its first few quarters on the market. On the bright side, it was terrific to see so much discussion of this therapy class at AADE, with diabetes educators reviewing the clinical safety/efficacy data and learning strategies on how to initiate Soliqua or Xultophy treatment in their patients. We were particularly intrigued during one Sanofi-sponsored dinner symposium, featuring powerhouse panelists Ms. Davida Kruger, Dr. Curtis Triplitt, and Dr. Maggie Powers. The trio pitched Soliqua and Xultophy as a way to circumvent the misconception from patients that taking more medications signifies diabetes failure. They listed this misconception as one of the major barriers to advancing a patient’s treatment regimen. The mental association of insulin initiation with failure is particularly sharp for many people with type 2, which is why basal insulin therapy is often delayed well past when it would be most beneficial. Soliqua or Xultophy, on the other hand, could be presented as a newly-available option free of these associations. Dr. Powers suggested that either drug be characterized to patients as an “adjunct” treatment, something that offers superior glucose-lowering compared to basal insulin or GLP-1 alone. We’ll be eager to see this tactic implemented in real-world clinical settings, to push the needle on commercial uptake of basal insulin/GLP-1 products. Dr. Kittie Wyne emphasized how combo therapy allows you to target many aspects of the “ominous octet” (if not all eight) at once, echoing Dr. Susan Cornell’s perspective from Pharmacology Boot Camp the previous day. Dr. Wyne presented basal insulin/GLP-1 products as a key piece in getting more type 2 diabetes patients to goal (in line with AACE algorithms, which recommend earlier, more aggressive intervention toward lower A1c targets). We note that the ADA’s 2017 Standards of Care document also recommends this new therapy class within the context of combination therapy. There seem to be so many arguments in favor of this therapy class.

Strategies to Avoid “Over-Basalization” Take Center Stage

• We heard several criticisms of the “over-basalization” epidemic in type 2 diabetes, with speakers urging the addition of other agents as an intensification strategy to address postprandial excursions – whether the traditional strategy of rapid-acting insulin, or instead newer agents such as SGLT-2 inhibitors, GLP-1 agonists, or basal insulin/GLP-1 agonist fixed-ratio combinations. UCSD’s Dr. Nathan Painter underscored that the efficacy of basal insulin decreases after the dose exceeds 0.5 units/kg, and larger doses only increase the patient’s risk of weight gain and hypoglycemia without providing additional benefit in A1c-lowering or postprandial glucose control. “We have to stop pushing basal up,” he argued, noting that his intensification agent of choice is a GLP-1 agonist, given the strong association with weight reduction. An entire corporate symposium was dedicated to the use of basal insulin/GLP-1 agonist fixed-ratio combinations as a basal insulin intensification strategy. An all-star panel featuring Ms. Davida Kruger, Dr. Curtis Triplitt, and Dr. Maggie Powers explained how switching from basal insulin monotherapy to a fixed-ratio combination such as Sanofi’s Soliqua (insulin glargine/lixisenatide) or Novo Nordisk’s Xultophy (insulin degludec/liraglutide) would have a similar effect to adding a GLP-1 agonist on top of basal insulin therapy, while reducing injection burden, co-pay burden, and logistically the number of prescriptions the patient needs to fill. Moreover, the speakers intriguingly suggested that these newer therapies, with their combination of multiple agents, might be able to circumvent the common misconception from patients that taking more medications signifies diabetes failure. Poor reimbursement is one obstacle, but reluctance from HCPs to prescribe a fixed-ratio combination (or even a GLP-1 agonist or SGLT-2 inhibitor) should not be a factor restricting patients from access to these advanced, highly-effective therapeutic agents. We’d love for all patients and providers alike to be well-informed about this new treatment option, especially in light of the diminishing returns of continually increased basal insulin doses. We look very forward to a (distant) future where these agents are generic and more widely accessible.

Diminished Focus on Obesity

• We were surprised (and disappointed) to hear very little on obesity at this year’s AADE meeting, despite the inextricable link between obesity and type 2 diabetes. What little we did hear on obesity related to matters of stigma. In a compelling session on why words matter, Dr. Jane Dickinson, Dr. Susan Guzman, and Ms. Melinda Maryniuk cautioned the audience against using “obese” as an adjective, advocating instead for less stigmatizing language such as “person with obesity” or simply stating an individual’s BMI. This was complemented by a talk on weight bias from obesity expert Mr. Ted Kyle, who pointed out that even healthcare professionals hold negative unconscious assumptions about people with obesity, associating obesity with words like non-compliant, lazy, lacking self-control, weak-willed, sloppy, unsuccessful, unintelligent, and dishonest, using this as the backdrop for a call for greater scientific rigor and empathy in obesity care. While these are extremely valuable points, we found the lack of practical discussion on obesity treatment as a missed opportunity to address chronic weight management as both a treatment and a prevention strategy in the context of type 2 diabetes. Too often the standard of care in obesity is no care, and beyond addressing the issue of weight more frequently (and in kinder language), providers need to be armed with the tools and the latest, evidence-based information to help their patients actually achieve weight loss.
• Furthermore, not a single obesity company was represented in the vast AADE exhibit hall. Even obesity market-leader Saxenda (liraglutide 3.0 mg) was entirely absent from Novo Nordisk’s booth, despite its status as a noted growth driver for the company’s pharmaceutical business as a whole and despite starring in a dedicated booth of its own at several recent meetings (including ADA, AACE, and ENDO). Again, we see this as a missed opportunity to educate front-line providers about available treatment options for obesity that go beyond lifestyle modification and combat the stigma and under-prescription of these therapies.

Big Picture

Outcomes Beyond A1c

• In a single packed morning, we heard from Adam Brown, Richard Wood, Dr. David Marrero, and Dr. Aaron Kowalski on the outcomes beyond A1c movement. It was a fascinating quartet, as they all took slightly different approaches in describing the need to move beyond A1c and adopt other outcome measures – especially CGM-based metrics. Using his own experience living with diabetes, Mr. Brown discussed the link between time in range and emotional wellbeing, recent progress toward consensus on CGM metrics, and speculated on how care might evolve in a post-A1c-centric, technology-driven era. Mr. Wood presented dQ&A survey data emphasizing the inability of A1c to capture the holistic impact of diabetes on quality of life. Meanwhile, Dr. Marrero explored the importance and complexities of health-related quality of life in diabetes, and Dr. Kowalski gave an impassioned address about other outcomes and the tradeoffs inherent to diabetes therapeutic choices. The talks really resonated with this group of attendees, who seemed eager to go beyond A1c based on their experiences with patients – there is so much more that is relevant in daily life with diabetes. Other speakers, such as Dr. Rich Bergenstal, Ms. Sharon Watts, Dr. Jennifer Sherr, also digressed to talk about the BeyondA1c movement in their talks. We loved to see the focus on this rapidly-advancing movement at AADE, and look forward to more at next month’s EASD (particularly on hypoglycemia) and at December’s IDF.

Cost Determines Care

• An inescapable theme at AADE 2017 was that cost is a big – if not the biggest – driver of what treatment a patient receives. At her third annual Pharmacology Boot Camp (a pre-conference session), Dr. Susan Cornell emphasized the many benefits to GLP-1 agonists in addressing six of the dysfunctional organs in the “ominous octet,” only to share that she herself still prescribes sulfonylureas: “The only reason I still use them is because they’re cheap, and I can send my patients to Walmart to get them for $4.” The overwhelming chatter among CDEs and nurses in the room, while acknowledging the profound efficacy of the GLP-1 and SGLT-2 classes, was that they cannot prescribe these agents to their patients because most won’t be able to afford them. We continue to be disappointed that such effective glucose-lowering, weight loss-promoting, potentially cardioprotective therapies are out of reach for so many. On the tech side, Dr. Michelle Litchman’s Instagram-mining revealed not only that patients often don’t wear CGM on the FDA-approved abdomen, but that they often wear them for longer than seven days, due primarily to cost concerns. Our own Mr. Adam Brown reminded HCPs to consider cost when helping patients choose devices, and when talking to representatives about prescribing their devices. Ultimately, HCPs who want to practice evidence-based medicine and employ advanced therapies face a substantial obstacle in cost (and poor reimbursement). After all, patients can only take the drugs they can afford – a seemingly simple idea, and yet one that we can’t emphasize enough. More needs to be done, and fast, on improving reimbursement, patient assistance programs, and the reach of public insurance to make advanced medicines affordable, and to support DSME and other valuable psychosocial supports.

CDEs as the Front-Line Change-Makers

• AADE speakers frequently emphasized the key role CDEs play as front-line change-makers in the diabetes world. Joslin’s Dr. Robert Gabbay gave a well-received talk on the shift to value-based care and how it creates a new role for diabetes educators. In the shifting healthcare reimbursement paradigm, from fee-for-service to value-based care, diabetes education moves from a cost center to a savings center (because it works to prevent complications and costs less money) – it’s no wonder so many audience members commented and tweeted that this presentation should have been a keynote! Diabetes educators have the opportunity to innovate and show their value in preventing costly complications down the line. In a similar vein, Dr. Julie Gee presented original research demonstrating the value of diabetes educators in patient-centric care, as they invite the patient to be a shared decision-maker: “Basically, CDEs rock – that’s what I found.” It was clear that AADE attendees greatly appreciated Dr. Gee’s survey and research, as one audience member commented, “We’re changing lives, but nobody knows that and nobody values us. CDEs are being scrapped in many health centers. We need to promote this information and educate everyone out there about who we are.” 
• Overall, AADE 2017 made it clear that diabetes educators do critical work in empowering patients, yet they are continually undervalued and even eliminated in health centers. The last day of AADE kicked-off with a panel of thought leaders, including Fit4D’s Mr. David Weingard, CDC’s Dr. Ann Albright, and our very own Mr. Adam Brown, who drove home this sentiment. Mr. Weingard summed up the theme quite nicely, “The reality is that primary care practices are being measured on quality – that they don’t have time to achieve – and the more all of you can help them achieve quality, and show them how you’ve changed the quality measures in the practice, the more you should be paid.”

Heightened Focus on Prevention, Starting with Debut of New CDC Ad Campaign

• Most exciting on the prevention front, CDC’s Dr. Ann Albright presented the agency’s revamped ad campaign for prediabetes awareness. This follows the first-ever national PSA targeting prediabetes from the CDC, ADA, AMA and Ad Council in January 2016, and this iteration (released in late July 2017) is centered around the same risk assessment, though this time there is no voice over (only text) and we’re treated to cute animal videos. Dr. Albright announced that >one million people (!) took the prediabetes risk assessment test in response to the 2016 PSA, which speaks to the tremendous influence of the CDC – we can’t say enough how glad we are that diabetes prevention has become a larger part of CDC’s agenda, with public awareness initiatives, support for the DPP, etc. That said, considering 84 million Americans have prediabetes and only 12% are aware of it, there’s still a lot of work to be done in terms of public health education and increased diagnosis. To this end, we were pleased to attend sessions at AADE focused on innovative approaches to prediabetes: ADA’s Dr. Erika Berg spoke to opportunities for precision medicine in identifying which individuals will benefit most from metformin vs. lifestyle intervention (two arms of the DPP), which fits in well with the increasing commentary we’ve heard of-late on risk stratification to make diabetes prevention cost-effective at the population level. In a talk on DSME, CDC’s Dr. Magon Saunders mentioned the urgent need to spread any diabetes-related public health intervention to rural populations, which are greatly underserved and which are driving the prediabetes and type 2 epidemics. In the same pre-conference session featuring the brand-new ads, individuals working tirelessly to improve prevention efforts spoke to their own experiences running a National DPP for diverse populations, and we liked that educators got to hear practical tips for success for different circumstances. A common sentiment was the importance of making the program accessible and fun, engaging participants and customizing sessions as much as possible. While this year’s prevention focus didn’t quite reach the same level as AADE 2016, with its dedicated Prediabetes Day, we heard very productive conversations on the whole. We left feeling cautiously optimistic after learning of real-world DPP successes and the widespread impact of CDC’s PSAs.

Emphasis on Psychosocial Care in Diabetes

• We were pleased by the emphasis on psychosocial care as an important dimension of diabetes management, given the prevalence of depression within this patient population, as well as of diabetes distress. Clinical psychologist Dr. Mary de Groot outlined that as many as one in four people with diabetes will develop depression – twice the rate of the general population. Equally troubling is that 38%-45% of people with diabetes report moderate to high levels of diabetes distress, a condition characterized by loss of motivation for self-care behaviors and inability to maintain an intensive treatment regimen. Beyond taking a significant toll on mental well-being and quality of life, the impact of depression and distress in people with diabetes is worsened glycemic control, decreased adherence to medication, and greater severity of diabetes complications – leading to increased medical costs, greater functional disability, and elevated rates of premature all-cause mortality. In a separate session, Ms. Terry Compton and Dr. Mandy Reece noted that the issue of psychosocial care is of paramount importance in elderly patients, who have a particularly elevated risk of depression as well as cognitive impairment (which could greatly complicate diabetes management). We couldn’t agree more that much better psychosocial support is critical to improve diabetes care for all patients, especially in light of the reality that a majority of diabetes management is self-management.
• The ADA’s new Position Statement on Psychosocial Care, written in collaboration with the American Psychological Association (APA), marks an important first step in defining best practices, general recommendations, and future aspirations for how psychological care should be delivered within the context of diabetes management. Dr. de Groot, an author of the document, outlined that the core philosophy underlying this document is that psychosocial factors in diabetes exist along a continuum, ranging from adaptive/healthy behaviors to diagnosable behavioral health disorders. For instance, a patient’s attitude toward hypoglycemia could range from healthy awareness to a paralyzing fear that impedes optimal blood glucose management. Against this backdrop, the position statement outlines five key recommendations: (i) Integrating psychosocial support into the medical care of all people with diabetes to improve both health outcomes and quality of life; (ii) Regular screening for diabetes distress, depression, anxiety, disordered eating, and cognitive capacity; (iii) Close monitoring of the performance of self-management behaviors as a window into psychosocial factors potentially affecting diabetes management; (iv) Considering the patient’s life circumstances and incorporating this into diabetes management strategies; and (v) Addressing psychosocial issues immediately with follow-up from a behavioral health provider.
• On the treatment front, the Program ACTIVE II study demonstrated the efficacy of a combination of exercise and cognitive behavioral therapy (CBT) for both resolving the symptoms of depression and lowering A1c in people with diabetes. The capacity of this combined intervention to lower A1c is a new and very exciting development from the original presentation of the study at ADA 2017. The combination of exercise and CBT reduced A1c by an average of 1.3% in individuals with a starting A1c >7% (p=0.02); neither intervention alone had a significant A1c-lowering effect. Notably, this study enrolled adults from diverse income levels and educational backgrounds (each of which independently affects psychosocial health) in both urban and rural areas.  This underscores that not only are Program ACTIVE II tools effective in the treatment of comorbid diabetes and depression, they are also generalizable to a wide range of underserved areas in the US.
• Though increased discussion on psychosocial care in diabetes is certainly welcome, we’re especially eager to observe a corresponding change in real-world clinical settings in the years to come. This will take some time, but it is increasingly clear that CDEs, as the frontline diabetes care providers, are uniquely well-positioned to turn the tide toward greater recognition of the psychosocial dimension of diabetes.

AADE Attendance Nears 3,000 People, >60% with 10+ Years of CDE Experience

• Attendance at AADE reached nearly 3,000 in 2017, down slightly from 3,600 in 2016 when the conference was held in San Diego. The conference drew an experienced crowd: a whopping 62% of attendees boasted more than 10 years of experience in diabetes education, and 39% had been CDEs for more than 15 years. This speaks volumes about the commitment and huge depth of knowledge among CDEs, but also foreshadows a potential shortage of young CDEs entering the field (to the extent that attendance at AADE is representative of the field as a whole). Against the backdrop of ever-increasing diabetes rates, we wonder what would incentivize more people to become CDEs – a question that looms large in endocrinology as well.

Diabetes Technology

An Educator's Use of Outpatient Insulin Dosing Decision Support Software

Bruce W. Bode, MD (Atlanta Diabetes Associates, Atlanta, GA), Lisa Kiblinger (Atlanta Diabetes Associates, Atlanta, GA)

After Atlanta Diabetes Associates’ Dr. Bruce Bode (“the hardest working man in diabetes”) and Ms. Lisa Kiplinger overviewed the need for and promise of insulin dose titration software, Dr. Bode shared some speculation on the landscape. Dr. Bode believes all three insulin companies (Novo, Lilly, and Sanofi) are committed to get the doses of their insulin devices to go to the cloud ASAP, “hopefully by the end of 2018.” Dr. Bode noted that Novo Nordisk is working with their own disposable pens, Sanofi is working with pen caps, and Lilly is working with pen cartridges with Companion Medical. We were interested to hear the news of Novo Nordisk’s work on disposable pens, since doing so would seem like an enormous disposable device change/addition in just 17 months! That Sanofi and Lilly are working on this was not surprising, given respective work with Common Sensing and Verily (Sanofi) and Companion Medical (Lilly). More details from our recent coverage are below. Dr. Bode also noted that Glytec is working with multiple companies to incorporate continuous glucose data into its titration software – great to hear, since current iterations only use BGM data. We’re glad to hear of all of these – given the dire need to use insulin more intelligently through data – though the field needs these to move to commercialization, scale, reimbursement, and outcomes. Many have been calling for dose capture for years, but no products are widely available yet (Companion Medical’s InPen might be the first, expected to launch this year following FDA clearance in 2016).

• We learned recently that Novo Nordisk is piloting a Novo Pen 5 Plus with NFC capabilities at 10 clinics in Sweden – Bluetooth is in the roadmap, which is clearly needed to realize the true vision of continuous, hassle-free data upload and continuous titration. For now, NFC on the Novo Pen 5 Plus enables data upload via a Glooko/Diasend NFC pad. We’re glad to see Novo Nordisk taking its first steps in digital health, including launching a data analysis and education app with Glooko two weeks ago (Cornerstones4Care Powered by Glooko). The company’s new digital health unit must be learning a lot and we hope to see big things from its collaborations with Glooko and eventually IBM Watson.
  
  • Dr. Bode’s point did bring up a good question: Which will patients prefer – disposable pens with connectivity via attachments/caps (e.g., BD’s smart pen needles, Bigfoot/Timesulin dose capture device, Common Sensing) or durable/reusable pens with connectivity built right in (e.g., Companion Medical InPen). Where can a more sustainable business model be built? What will patients, providers, and payers be willing to pay for? What is lower hassle in the current healthcare systems around the world? How valuable will insulin dose data be and what device price premium might it command? Will connectivity + paired apps emerge as a competitive advantage for different insulins, or will insulins become a commodity and the true differentiator will actually be the apps/education built around them? We are huge proponents of this field and hope to see many, many products launch for capturing the dose data and using it effectively!
• Glytec’s outpatient eGlycemic Management System (eGMS) is currently partnered with Telcare, Livongo, and Agamatrix, and according to Dr. Bode, the company would consider a collaboration with any company that has a connected BGM – no surprise there, since passive glucose data collection is essential for making this product simple and low burden. However, our interest was piqued to hear that Glytec may be working with Abbott and Dexcom – Dr. Bode mentioned that Glytec’s system might even automatically titrate insulin retrospectively using professional CGM data. The growing body of literature on titration has shown that basing adjustments solely on SMBG data is very effective, but we can only imagine that the depth and breadth of glucose data offered by CGM would result in even better outcomes. As a reminder, Bigfoot acquired Timesulin in June and partnered with Abbott last month, giving it all of the pieces required to generate insulin dosing recommendations for MDIs based on continuous glucose data. Said Ms. Kiplinger, “You see the FDA clearance dates for these products are almost all 2017 … the field has really rapidly changed. Last time this happened was when the Internet came about.”  
• It’s no surprise that Sanofi and Lilly are actively exploring the development of connected pens and caps. Sanofi has invested in Common Sensing (Gocap manufacturer – very exciting data at ADA), and Lilly has invested in Companion Medical (FDA-cleared InPen manufacturer; launch most recently expected this year). Further, both companies have embraced dose titration via apps (see Sanofi’s My Dose Coach and Voluntis partnership and Lilly’s Go Dose), and enhancing these systems with passive dose capture makes logical sense. It will be interesting to watch these three pharmaceutical giants enter the tech field – at what pace will products come out, how will the companies outsource vs. build internally, and how will they maintain products over time in an ever-changing app world? The insulin players know how to compete on drug products, but the tech world is a giant cultural shift. How will this play out? We assume once one major player launches a connected pen, the others will most certainly have no choice but to follow. Right now, it’s a question of game theory – who will be first? Connected pens feel inevitable at this stage – undoubtedly a “when” more than an “if” – meaning all three should be investing in connected delivery devices now; the R&D must be ready to translate to commercialization in the next couple years. Passive dose capture paired with glucose data and titration software strikes us as one of the richest areas for insulin innovation – and far less expensive and risky than bringing a brand-new insulin to market (though we’ll take that too).
• According to Dr. Bode, Glytec’s subcutaneous inpatient Glucommander was used to treat over 150,000 patients this year, more than doubling since last year! The system is clearly very scalable, and based on retrospective data presented at that same ATTD presentation, is proving effective – patients (n=5,718) admitted with hyperglycemia to one of seven hospitals arrived at their prescribed target blood glucose in 0.8 days from a starting average of 262 mg/dl. Once at target, 68% of blood glucose readings remained between 70-180 mg/dl. Hypoglycemia was very unlikely once target had been reached and in the next 24 hours, with just 0.001% of time below 40 mg/dl and 0.01% of time below 70 mg/dl, respectively. Wow!
• Dr. Bode reminded the audience that “it’s a dosing problem, not an insulin problem.” Patients frequently discontinue their insulin regimens due to a number of barriers, and if they didn’t, the US health system could save an estimated ~$5,000 per patient per year – assuming 30% of people with diabetes take insulin, that adds up to a shocking $45 BILLION per year! He rattled off a number of alarming statistics, even for those following the field: 31% of patients never fill their script; only 50% modify their dose after an episode of hypoglycemia; 40%-60% experience hypoglycemia; 40% experience hypoglycemia in the first month; 50% of patients taking basal insulin are not at their A1c goal; and 77% discontinue insulin within 12 months if they experience hypoglycemia in the first six months. Not only could insulin dose titration make dosing of insulin safer and more effective, but it would also crucially make patients think that insulin is safer, resulting in better adherence, health, and cost savings.
• Using a titration software such as Glytec’s, Dr. Bode estimated that a CDE could feasibly monitor and treat up to 300 patients at any given time. Ms. Kiplinger explained that the duty of the educator (at least in her clinic) is to educate the patient (when and why to check blood glucose, how to use the system, what to expect), coordinate the care team, and monitor the patient (for safety). Since the software takes care of the rest, noting when a patient is in need of an adjustment and calculating the new dose, the educator simply has to fill in the cracks and support patients. We wonder how clinician-facing titration software will compare to those that are patient-facing – do the former offer a better framework to support the user, resulting in better engagement? Patients-facing software that mostly runs on its own is more scalable, but will drop-off be higher?

Let’s Get Digital

Chris Bergstrom (Boston Consulting Group, Boston, MA)

In a whirlwind keynote entitled “Let’s Get Digital,” BCG’s Mr. Chris Bergstrom (with some help from videos of some well- known educators and one CEO), instilled confidence that we are in the midst of a monumental transition in the way diabetes is managed, thanks to the rise of digital health. To a packed general session, he touched on the rapid pace of innovation, new sources of big data and how it’s being used, the explosion of partnerships in diabetes industry, enthusiasm for augmented reality, and a few of the digital health tools that are already here. A core theme throughout his talk and the videos was “New tools. Same hands.” A powerful point of view that emphasizes the need for educators is not going away, quite the opposite, but their role in the future, will necessitate the use of digital tools. He concluded with a call to action for educators in the audience: “Take a leadership role to experiment with these digital health solutions, provide feedback to the patients who are using them and the people who are making them. Use them to reach more patients than you ever have. Basically, be superhuman.” The talk was certainly persuasive – Mr. Bergstrom was told that attendance at some of the digital health booths was up 10x after his talk!

• “Every single one of the largest companies [in the world] is a technology or digital health company.” In 2001, just one of the top five largest public companies in the world (by market cap), was digital – Microsoft. Today, just 16 years later, Microsoft is still there, but joined by Apple, Alphabet, Facebook and Amazon (displacing GE, Exxon, Citi, and Walmart). Mr. Bergstrom noted that most of the technology companies at the pinnacle of the market are moving into healthcare in a big way, attacking longstanding health issues in a different way, using different tools. His slide below implied the rate of adoption of new technologies will accelerate. While it took 46 years for electricity to take hold (defined as use by 25% of Americans) and 35 years for the telephone, it only took seven years for internet and five for social media. What’s next? Since the ubiquity of internet and social media is causing rapid and mass dissemination of ideas, we imagine that this curve hasn’t nearly bottomed out yet. We wonder where the smartphone would fit – last year, nine years after the iPhone launched, Pew Research Center says 77% of Americans own one – wow!

• In the first half of this year, Rock Health’s midyear review indicated an explosion in digital health venture capital funding. Mr. Bergstrom cut the data by diabetes area. The slide below shows the category of diabetes therapy garnering the most VC interest in 2016: Digital Health and connected BGM topped the list (at ~$450 million), followed by CGM, non-invasive tech, PoC diagnostics, care management/community engagement/education, and lastly, traditional glucose monitoring. The ordering is not unexpected today, but Mr. Bergstrom made the very astute observation that this likely would have been upside down just 5-10 years ago. We’re not sure who the ~$450 million went to in the first category – the big ones that come to mind are Livongo’s $44.5 million round , WellDoc’s $29.5 million Series B, and Intuity Medical’s $40 million round.  

• We’re seeing “a bit of an arms race, or at least a race to the prom with the best date!” He further explained, “marrying those who can innovate quickly with those that can scale globally is what digital needs today. It won’t be easy, but it’s necessary, and it’s happening.” The slide below does a good job summarizing what we’ve been saying for the past couple of years – partnerships between players big and small seem to be accelerating. As one keen twitter observer noted, “some very strange bedfellows!” In fact, to illustrate how strange, Mr Bergstrom shared an analogy of building a car where large healthcare companies would take a long, but direct route. Whereas, the digital companies would take an iterative, rapid, “AGILE” route that gathers real-world input via “minimal viable prototypes”. We’d also note that Lilly is an investor in Companion Medical and Beta Bionics and Ascensia has an integration with Voluntis. BD is definitely committed to digital health (it launched an app, Leah earlier this year), though it seems to be working more internally at this stage. 

• According to Mr. Bergstrom, patients need four levels of support: Face2Face, Remote, Automated, and Peer2Peer. Face2Face has been in existence since the dawn of man, but only recently has the rest of the pyramid been unlocked by connectivity (“finally!”) and data storage platforms. Within diabetes, Mr. Bergstrom was pleased to report that we are finally seeing connected glucose monitors on the market (using cellular, Bluetooth, headphone-jack, NFC, all of which provide a different user experience). While further behind, the innovation in connected insulin pens/pen attachments is heating-up (Timesulin – recently acquired by Bigfoot, GoCap, DataPen (we hadn’t heard of this one), InPen, and BD Smart Sense Pen Needles, and added that all big insulin companies are piloting and getting in on the game). We will soon even see connected pills (eTect, Proteus, Adhere Tech). There are also now places to store, visualize, and share that data, namely Tidepool and Glooko. He shared that the latter, as of July 2017, has over one million patients (47,000 Insulet users; same user base as shared in September), is used by 6,000 providers, and holds five billion diabetes data points.
  
  • In the remote tier, Mr. Bergstrom mentioned Fit4D and the subscription models emerging out of Livongo, One Drop, and mySugr. We like the unlimited strips + coaching model, which reduces patient hassle and gives 24/7 CDE access – all three of the latter companies are starting to generate early outcomes data, and the key will be in scaling it up and getting more and more payers on board. (Also worth noting here, during Nancy D'Hondt, President AADE, mentioned during her opening day keynote that BMS is sponsoring an RCT comparing traditional Face2Face DSMT with remote tele-DSMT. We can’t wait for those results and applaud AADE and BMS for adding to the evidence base for digital health.)
    • Livongo told Mr. Bergstrom that its CDE’s responded to 110,861 out-of-range blood glucose checks this spring, almost 22,000 of them low. This is part of the power of connectivity and remote coaching – how many adverse events, hospital trips, and deaths did these outreaches prevent, and how much money did they save? We hope CGM and connected BGM companies can start to illuminate the real-world patient experience and help validate metrics like time-in-range by connecting disparate data sets.
  • Within the automated tier, Mr. Bergstrom highlighted WellDoc’s BlueStar (where he was formerly Chief Commercial Officer) and iSage Rx. WellDoc’s BlueStar is an example of a mobile prescription therapy that turns data into knowledge – “We’ve turned software into a drug. It works, and it’s paid for.” WellDoc was notably the first mobile prescription therapy and it’s even noted as a separate class of therapy on ADA’s website. iSage Rx, on the other hand is very focused – it titrates all basal insulins – and provides education around the recommended doses. iSage Rx aspires to be the “Intel Inside,” to provide insulin titration as a service for the field (i.e. integrated into other products). We’ll be fascinated to see how it scales and when it’s more widely available. After the debut announcement in May, the company announced a partnership with Hygieia in June.
  • Lastly, in the Peer2Peer category, Mr. Bergstrom loves following HelpAround – the “mobile safety net” for people with diabetes. He can’t believe how high quality the advice that people share is, and is struck by the emotional support people receive from all over the world – he’s heard of people driving 40 miles to help a stranger. A big theme at this conference was peer support on social media – patients, caregivers, and clinicians are spending more and more time online to give and share advice.
• Mr. Bergstrom believes augmented reality (AR) will be a big deal, including in diabetes education, very soon. AR is immersive, real-time, and engaging, making it a very effective tool to potentially teach people with diabetes what is going on inside their bodies – where does insulin come from? Where does glucose go? Where do nerves get damaged? This can make a clinician’s words more real for the patient. He also brought up the potential for AR in automated carb counting – what if you looked at a plate of food with AR lenses on and they told you the carb content? We saw a version of this at DiabNext’s booth (see our exhibit call coverage), and were fairly impressed. We assume many companies are working on this internally, given what machine learning can do these days with photos (e.g., Google Photos, IBM Watson). In his talk later in the day, Adam Brown similarly suggested that educators might expect to use new modes of visualization and communication such as AR, virtual reality, and voice (Amazon Alexa) to convey education and scale it outside of face-to-face care. Mr. Bergstrom showed a fascinating clip of Microsoft’s HoloLens being deployed at Case Western Reserve University for medical education. Said one person in the video, “A click of the finger will allow the student to see how everything in the body is connected.” One of the biggest challenges with technology is clinical inertia, and we’ll be interested to see how doctors’ and educators’ offices adopt these latest trends.
• Big data is also coming to healthcare, noted Mr. Bergstrom. In the overarching technology landscape, companies like Google collected data, Facebook shared it, and IBM Watson is now using it to generate insights. In healthcare, according to Mr. Bergstrom, the equivalent entails digitizing file cabinets into EMRs and putting logbooks in the cloud (making it easy to share). Further, EMRs are now making app stores, Mr. Bergstrom said, and APIs are starting to open so systems can talk to each other. This process has taken longer in healthcare because of privacy and security concerns surrounding sensitive health data, but the interoperability of this information will unlock waves of innovating for “applying analytics to supercharge disease management.” To Mr. Bergstrom, this could take the form of automated coaching, predictive alerts, and clinical decision support – all of which we’re already beginning to see the first phases of! It could even help identify new clinical pathways, intervention protocols, and population health insights. It was announced that BCG has partnered with the AADE, NYU, and the State of New York, where BCG’s team of 300 data scientists will mine over 10 years of Medicaid claims for 12 million people, to uncover improved diabetes protocols.
  
  • In one of the coolest parts of the talk, Mr. Bergstrom demonstrated the power of social media-derived big data on patient-reported outcomes. The network in the slide below (top) represents ~6,000 posts from digital forums in which patients are complaining about diabetes. Each color corresponds to an area, such as air bubbles or sensor adhesive or skepticism. In his view, having this sort of information on hand could rapidly alert manufacturers and educators (and FDA and payers!) to pain points that need to be addressed. Pointing to the slide just below, Mr. Bergstrom then showed what it might look like if applied to a single practice. This sentiment analysis would allow comparison to other practices, opening up avenues for learning exchanges and proper allotment of resources. In this case, the featured clinic handles insulin pumps very well (green), but not so well with insulin injections (red). Wow! This would clearly put population health into action.

• Mr. Bergstrom’s lecture was infused with videos (produced by BCG and Havas) featuring testimony on digital health in diabetes practice from well-known educators Ms. Malinda Peeples (Past President AADE), Ms. Donna Ryan (President Elect AADE), Omada CEO Mr. Sean Duffy, and others. See immediately below for some of our favorite quotes.
  
  • “7% of people with diabetes see an educator. Even if we doubled that, 14% is still unacceptable…We have to leverage technology and our resources so we can touch everyone that needs support if we want to improve outcomes.” – Ms. Ryan
  • “Data alone is table stakes – it’s the ticket of entry. It gives you the ability to make an impact. How you use it, to provide context for the patient and CDE, will make all the difference.” – Mr. Duffy
  • “I feel safer when I make dosage adjustments because I see everything I need to see, not just blood glucose. I almost feel spoiled.” – Ms. Rebecca Crespi
  • “I’m more organized and I have more time to do what I want to do in and out of my practice.” – Ms. Susan Weiner
  • “The patient is taking a much more proactive role in diabetes management, where before they might’ve felt helpless.” – Ms. Cher Pastore
  • “Their blood glucoses are coming to range much more quickly, A1c, weight loss. Pretty much across the board, overall health is improving, but quality of life too.” – Ms. Brittny Small
  • “It’s now easier to fight with insurance companies to get supplies for people. Because now you have months and months of records.” – Ms. Crespi
  • “We’re getting to know patients much, much better. This is probably seeding precision medicine efforts more than anything else going on right now.” – Ms. Peeples

OpenAPS and DIY Diabetes

Dana Lewis (OpenAPS, Seattle, WA)

As always, Ms. Dana Lewis of OpenAPS provided an inspiring presentation on the ongoing efforts of the DIY diabetes tech community, highlighting recent developments including the “eating soon,” “autosensitivity,” and “autotune” features. The “eating soon” mode aims for a smoother meal ride by dosing with a small amount of insulin 45 minutes to an hour before eating. Ms. Lewis emphasized that this is not a pre-bolus, but instead a way for basal insulin to start ramping in preparation for a meal – the individual still takes a bolus at mealtime. For example, if the target is normally 100 mg/dl, pressing the “eating soon” button would set for a target of 80 mg/dl. In this way, if an individual ends up skipping a meal, there is a lower risk of hypoglycemia. (of course, it also requires giving the system a heads up an hour in advance.) Ms. Lewis cautioned that meals are usually a sticking point, and it takes some troubleshooting to customize the “eating soon” mode for each individual. The “autosensitivity” feature allows for real-time assessment of insulin sensitivity factor (ISF) and glycemic targets using the past 24 hours of data. This feature is particularly useful because sensitivity can change due to a dying pump site or when sick, thereby resulting in a different optimal ISF. For example, Ms. Lewis commented that her ISF changed dramatically due to travel for the conference and a different eating regimen. “Autotune,” shown in a poster presentation at ADA, is a pump settings optimizer – it recommends changes in basals, ISF, and carb ratio by drawing from a much larger pool of data. These variables are often determined through trial and error by a healthcare provider, but with this tool, an individual can get precise values calculated with their own data – wow! As Ms. Lewis pointed out, this will be especially useful for growing children

• Ms. Lewis hopes diabetes technology companies look at what the DIY community has achieved and think, “We should be doing at least that well if not better.” DIY loopers are not trained programmers, yet they are linking together devices, data, and algorithms that have radically changed lives. Ms. Lewis hopes the movement will push the industry and FDA, demonstrating exactly what they need and the lengths individuals will go to achieve it – we think it is already doing this and will continue to do so! Ms. Lewis sees ample room for improvement from industry, including the interoperability, remote monitoring, the ability to change glucose targets, and the incorporation of smart watches for added discretion. We agree on all those points!
• Many providers still refuse to discuss DIY looping with patients because it is off-label and not FDA approved. In some cases, providers will go so far as to terminate treatment. Whoa. To these clinicians, Ms. Lewis urges remembering that the patient is the one living with diabetes, and if a tool works, providers should be supportive. DIY looping requires a setup and maintenance commitment (it’s not a plug-and-play commercial product), and one that individuals are only likely to undergo if they’ve experienced tangible benefits.
• Ms. Lewis advised diabetes educators to take advantage of the open source community to learn more about how to best serve their patients who are looping. She pressed educators to read the documentation on openaps.org (there’s also Loopdocs.org) and ask questions – educators have the ability to reach thousands of patients and need to be equipped with as much knowledge as they can. Ms. Lewis also pointed that educators are likely to have more hands-on experience with this technology than physicians. She advised educators to partner with highly engaged patients, viewing them as a head start to educating those who are unaware of looping.
• We really enjoyed hearing Ms. Lewis’s origin story for OpenAPS, which included a five-hour-long first date, recommended hugs, and an emphasis on team effort. For Ms. Lewis, it all started with her diagnosis at age 14, which she likened to being struck by lightning. From there, her frustrations with the current state of diabetes data and technology led to her developing a closed loop system, in partnership with her now-husband Scott Leibrand and leveraging years of work from the brilliant Ben West (now at Dexcom). With an estimated 400+ people now looping (DIY closed-loop of all types – we assume this is an underestimate), Ms. Lewis serves as a reminder for the kind of impact small groups of individuals can have – as one audience member said, “She’s the smartest person I know.”

Questions & Answers

Ms. Amy Tenderich: Obviously the FDA is aware of this. Can you explain their current stance?

A: They’re hyper aware; they read my blog. They have chosen to exercise enforcement discretion. They verbally said, ‘we don’t think you should be doing that,’ (originally regarding sharing DIYPS, an open loop system) but open source code and documentation is free speech, and because we’re not doing anything commercially, we’re not doing anything regulated by the FDA. They encourage us to do what is safe, and we have such a rigorous safety approach – they’re on the same page as us. (Editor’s Note: Can we just applaud the FDA’s CDRH, yet again, for being so patient-friendly?”)

Dr. Perry Gee: What is your relationship with the various manufacturers that you’ve talked about?

A: We’ve had a lot of conversations with manufacturers – those companies are working on artificial pancreas technology that they’ve had in their pipelines for much longer. They’re burdened by the traditional system, where it takes 5-10 years to get to market. The first generations were designed 7-8 years ago, the second generation will be more like the device I’m wearing in terms of sophistication of algorithms. We tell them we want to make your products better. Some of them just listen, others do focus groups of communities who have been living with this technology (Editor’s Note: Insulet, per its ADA presentation at DData), which is really smart, and we’re hoping more will do that. We’ve learned so much about what information we need to have. Manufacturers have had great relationships with the open source community, there’s lot of knowledge inside companies about DIY (Editor’s Note: Dexcom hired Ben West and Chris Hannemann last year, Bigfoot has many DIYers in house, including co-founders Bryan Mazlish and Lane Desborough). We’re hoping to have more conversations. It’s all open source so any company could use the code. There are a lot of sophisticated features and algorithms we’ve developed that these companies should be learning from.

Diabetes Technology in the Wild: What Matters to Patients and How to Keep Up

Adam Brown (Senior Editor, diaTribe.org; Head, Diabetes Technology & Digital Health, Close Concerns, San Francisco, CA)

With characteristic enthusiasm, Adam Brown provided tips to educators on calibrating CGM, using pumps and automated insulin delivery effectively, and avoiding common pitfalls with all three technologies – download his slides here. Adam used his own diabetes data throughout and shared many examples of how small tweaks can have a big impact on device performance and glycemic outcomes  – washing hands or taking the second drop for calibration, “soaking” the sensor to really improve day one accuracy (more in-body time before a sensor start), using a highly accurate BGM for sensor calibration (FreeStyle Lite, Contour Next, AgaMatrix Jazz/Presto, Roche Accu-Chek Guide/Aviva Plus), and viewing glucose numbers as neutral information to make a decision (not a “test” or grade on diabetes performance). Adam emphasized the importance of managing patient expectations, whether for meters (“not perfectly accurate devices”) or automated insulin delivery (“YOU STILL HAVE TO BOLUS” and “System performance lives and dies with CGM accuracy”). He shared some learning from his experience on the DIY Loop system, highlighting excellent overnight control and some fascinating daytime cases where automation+his behavior resulted in lows or highs – AID still requires daytime planning, and patients need to adapt real-time behavior for treating lows (eat less), treating highs (smaller boluses), and dealing with meals/exercise (thinking ahead is still key). Adam emphasized throughout that in the rapidly accelerating diabetes technology world, educators will become even more important, not less. (He quoted Wired Co-Founder Kevin Kelly on the future of technology: “Productivity is for robots. What humans are going to be really good at is asking questions, being creative, and experiences.”) Towards the end of his talk, Adam gave tips for keeping up with new devices, questions to ask companies, and how to help people with diabetes pick a new device.

• Adam’s message on CGM calibration was clear: fingersticks drive CGM accuracy, and it is therefore critical to (i) wash hands before calibrating or (ii) wipe off the first drop of blood and use the second one (if washing hands isn’t possible, and it often isn’t!). Adam emphasized that BGMs are not perfectly accurate devices, something that surprises many people with diabetes. He drew laughs as he noted the new world of more accurate CGM – Adam is often using his sensor readings to double check that his meter is accurate, not the other way around. He recommended always washing hands and re-checking if the fingerstick and CGM differ by a wide margin. When there’s a huge mismatch, he said, it’s often because the meter is reading falsely high from dirty hands. These situations are of course the most dangerous, as an insulin dose on a false high can put people in the hospital.
• Adam cautioned that CGM is least accurate on day one and when blood glucose values are rapidly changing. To optimize day one accuracy, Adam recommended “soaking the sensor.” Day one of CGM wear is still a challenge, he noted, even with the most accurate devices on the market. To combat this, Adam puts a new sensor on three-six hours before his current sensor expires. However, he doesn’t start the new sensor or connect the transmitter; this way, it has longer to acclimate and it seems to dramatically improve accuracy off the bat. Adam also cautioned against over-calibration – in his experience wearing the Dexcom G5, it really only needs twice daily calibrations (one at wake-up, one before bed – also times where glucose is stable and handwashing is accessible). Patients are often tempted to over-calibrate, but if the readings from the BGM are not accurate, compounding errors can occur.
• Adam also touched on BGM accuracy, recommending several meters that have shown very accurate data: Abbott FreeStyle Lite, Ascensia Contour Next, AgaMatrix Jazz/Presto (CVS Advanced, Up&Up, One Drop), and Roche Accu-Chek Guide or Aviva Plus. Adam shared the link to the recently released DTS  BGM surveillance study, recommending it as a resource for more information. Concerningly, he noted that ~62% of Medicare BGM claims last year were for meters that did not pass DTS’ accuracy bar – many heads nodded in agreement. To ensure a device’s accuracy, Mr. Brown suggested that educators look at device’s proportion of readings within 10 mg/dl or 10% of the lab value – a good mark, he said, is 85%+.
• Adam cautioned against the “rage bolus” with CGM – educators must remind patients that it takes time for insulin to act, and it’s tempting to stack insulin with CGM (particularly if alarms keep going off). CGM tends to lag when recovering from hypoglycemia, another important clinical pearl – it’s easy to overeat when recovering from a low, since the CGM may read low but glucose will be back in range.
• For automated insulin delivery systems, Adam noted the importance of setting patient expectations (basal automation doesn’t impact glucose quickly), calibrating well (“System performance lives and dies with CGM accuracy”), and letting systems handle moderate highs and lows. As Adam has experienced himself, closed loop devices significantly improve nighttime glycemic control, a selling point that should be emphasized with patients. He also showed an example of how this strongly ripples into the next day and affects productivity, breakfast decisions, etc. Still, Adam noted that patient behavior must adapt during the day: users accustomed to micro-managing their diabetes will have to refrain from tinkering with the system, since doing so tends to drive rollercoaster glycemic outcomes. Lows typically require less treatment, since the pump has been suspended; highs may require less insulin for correction, since basal has already been increased. He added, “Exercise still needs pre-planning – temp target at least one hour in advance or turn off closed loop” and “YOU STILL HAVE TO BOLUS, unless eating fewer carbs (<20 grams at one time, high-fiber/fat).”
  
  • Like many closed loop users, Adam has been impressed with the overnight glycemic benefits. “I did not expect to see this much improvement.” He added, “It’s insane to have one basal every night,” a point we’ve also heard in recent 670G product theaters. Indeed, when looking at automated insulin delivery studies, Adam said, the variability is crystal clear – sometimes systems give half a patient’s usual overnight dose, and sometimes they give twice as much! (Dr. Roman Hovorka calls this “controller effort.”)
• Adam also highlighted some of the insulin pump mistakes he often sees (or makes himself): (i) take into account insulin-on-board; (ii) bolus 20 minutes before eating (Adam said one of the reasons he chooses to eat fewer carbs is that it’s hard to remember to do this); and (iii) do not suspend the pump to avoid hypoglycemia (a common mistake). For treating low, Adam suggested a go-to, automatic hypoglycemia correction like glucose tabs ­– “They’re easy to dose, I know exactly how many I need to eat, I’m not going to over-eat glucose tabs, and I don’t have to think. If you go to the fridge when you’re low, it’s game over.” Adam also advised rotating pump sites to avoid lipohypertophy (“BD has done some compelling work on reusing the same sites”), holding the pump vertically when priming to ensure air bubbles escape, and using an inserter (something he learned wearing the BD/Medtronic MiniMed Pro-set.
• When helping a patient choose a device, Adam recommended what he referred to as the “Big Three” drivers: (i) cost; (ii) options; and (iii) “TRY” (TEST devices; READ reviews; and “YOUR patients’ diabetes – it may not stick). Adam noted other factors that may influence the decision too: On-body size and feel; ease of use/complexity; ‘cool factor’; connectivity, data upload, remote monitoring; compatibility (e.g., iPhone vs. Android); screen size, touch (dexterity, vision); data displays and reports; and the company’s product pipeline. For more information on the latest devices, Adam advised educators to subscribe to diaTribe.org.
• Adam expressed frustration that test driving a car before buying is common, while test driving a new diabetes device before buying is not. While it can be difficult to test devices personally, Adam encouraged educators in the room to ask companies for test drive programs. He did share that some companies have a 30-day return policies, but these are not really promoted and they still require buying the device, getting the prescription, and processing insurance.
• “Company websites: a great starting point, but often not comprehensive or ‘real world.’” Adam cautioned educators that company websites are excellent for the basics of a particular product (what does it look like; key features, new/different features; links to phone apps, guides, and FAQs), though they’re not ideal when it comes to the true user experience (what does it FEEL like to use?), real-life hassles (How does it fit into daily life?), drawbacks, honest comparisons to other devices, and cost (in most cases).
• When talking to representatives, Adam advised the following: (i) Ask to use the device! Hands-on experience is critical. (ii) How much does it cost? Are there copay assistance programs available? (iii) What most distinguishes this device from others in this category? (iv) What are some of the top criticisms you hear of this device? (v) Who is this device best suited for? Who is not a good candidate? (vi) What is required for setup and training? (vii) What products are coming next from your company, and what is the upgrade path to get them?
• Adam compared glucose readings to cockpit sensors used to fly a plane – if a pilot gets an out-of-range reading, they’re going to act and change how the plane is flying. “Seeing that the plane is off course, a pilot would not say, ‘I’m a bad pilot.’ They would act on the reading and move on. We should be doing the same thing in diabetes with glucose data!” He emphasized that blood glucose data should be treated as neutral information to help people make decisions. When providers talk about blood glucose “tests,” it implies the number is a grade – this can easily make patients feel like a failure and drive less glucose checking. Adam polices himself constantly to say “check glucose,” and advises putting a sticker on the meter that says, “It’s just a number.” For more on this point, see the Mindset chapter of his book, Bright Spots & Landmines: The Diabetes Guide I Wish Someone Had Handed Me.
• Adam noted that Amazon reviews are increasingly becoming another area to source input on devices. He showed a picture of Contour Next strips on Amazon, which have a remarkable 900+ reviews and are available at a very inexpensive price. “But it’s important to keep in mind the Yelp effect: individuals with spectacular and awful experiences are often the ones reporting their views.”

MiniMed 670G System With SmartGuard (TM) HCL Technology: Driving Patient Outcomes Through Automation

Jennifer Sherr, MD, PhD (Yale University, New Haven, CT) & Trish Comrie-Sheer (Medtronic, East Lyme, CT)

Yale’s Dr. Jennifer Sherr shared her enthusiasm for use of the MiniMed 670G in adolescents, as well as the moment she realized the power of automated basal insulin delivery. She was most excited about the adolescent data from the 670G pivotal study, noting that “teenagers are going to be teenagers,” and the hybrid closed loop system should enable improved glycemic control, while still allowing young patients to be themselves. (In addition to overnight, the big benefit in teens in the pivotal came in stemming post-breakfast highs.) Indeed, the 670G pivotal found that adolescents were in Auto Mode a solid 76% of the time (vs. 88% in adults), which stayed roughly consistent in real-world use at the Barbara Davis Center in one-year data (ADA 2017). In the recent customer training phase, median time in Auto Mode in ALL users improved to 92%, though adolescent-only data was not broken out. Like other 670G prescribers we’ve heard from, Dr. Sherr was particularly taken with the tight control achieved overnight via dynamic insulin delivery. Her lightbulb moment came when she was looking at a patient’s data and realized that insulin delivery was halted for two whole hours. In her own words, “I agonize over basal rates, and I realized there’s no way I can get this degree of control [with manual insulin adjustments].”

• Dr. Sherr wrapped up her presentation with a brief discussion of the limitations and strengths of the pivotal trial, acknowledging that the lack of a control group and imbalance between the two-week run-in and three-month study phase data are problematic. Still, the data was collected over a broad age-range at 10 centers and strongly suggests the 670G to be a safe and effective device, at least in the engaged group in this study.
• In the coming years, we hope to see Medtronic’s closed-loop devices move to simplifying the user interface, optimizing training and prescribing, minimizing daytime user burden and improving control further (e.g., automatic correction boluses), reducing sensor calibrations, adding Bluetooth and smartphone connectivity, personalizing algorithms further, and dropping costs.
• Dr. Sherr was impressed with the new features of the 670G, highlighting the highly accurate Contour Next Link 2.4 BGM. The automatic wireless transmission of blood glucose data to the pump minimizes entry errors and shaves seconds off diabetes management time. It’s also a major plus to have this highly accurate meter driving calibration for the Guardian Sensor 3. While a few seconds might not seem significant, as Dr. Sherr noted, when managing a chronic disease over a lifetime, every few seconds really count.
• As a reminder, Medtronic has had some sensor shortages near-term, which are presumably gating a wider launch of the system to the full 20,000+ Priority Access Program participants. As of Keystone in mid-July, ~1,000 patients had used the 670G, implying it had reached a couple hundred additional people beyond the Customer Training Phase (~750 people) and pivotal study (124 participants).
• Dr. Sherr kicked off the 6 AM symposium with the infamous T1D Exchange curve indicating that only 25% of patients with type 1 diabetes are reaching their A1c goal. To our delight, she added that it may be time to move beyond A1c and talk about other metrics like time-in-range, referencing a conference “last month” (the Glycemic Outcomes Beyond A1c Workshop hosted by the diaTribe Foundation). Indeed, we’d love to see benchmark data on T1D Exchange registry members – what fraction spend 25%, 50%, 75%, and >75% of the day in 70-180 mg/dl?

Ms. Trish Comrie-Scheer provided valuable teaching tips for patients on the 670G system, focusing on setting realistic expectations and fostering trust in the system. As we have heard time and time again (recently during a panel at Keystone), it’s critical that patient expectations of hybrid closed loop systems are managed appropriately. Ms. Comrie-Scheer suggested emphasizing that this is not a panacea designed to eliminate all user interaction; patients are still responsible for mealtime boluses and correction doses, as well as calibration, setting temporary targets for exercise (if desired), etc. In fact, like many new devices, 670G demands a higher level of engagement at first, and it will be important to remind patients of this before starting the system. She also recommended explaining to patients that glucose levels will not be perfect, and the system will initially be conservative, titrating insulin delivery in a more personalized manner over time. (Previous total daily doses inform the algorithm’s aggressiveness.) Echoing commonly held sentiments, Ms. Comrie-Scheer discussed the difficulties in encouraging patients “to let it ride” – trusting the system can often be challenging for patients accustomed to aggressively managing their diabetes. She suggested reminding patients that the algorithm is usually smarter than we are, and that it may act to normalize blood glucose more slowly than patients are used to (actually a benefit, considering the dangers of insulin stacking and rage boluses). According to Ms. Comrie-Scheer, patients may also initially struggle with new terminology; many are used to religiously monitoring A1c levels, thus making the interpretation of time-in-range a difficult transition requiring new skills and training. She further advised providers to educate patients on how to analyze percent time spent in the low and high glucose ranges – we hope to see robust training materials and guidance built out on this front.

• Ms. Comrie-Scheer provided a touching case study of a 14-year-old type 1 patient, who achieved massive improvements using the 670G – time-in-range increased by seven hours per day (from 44% to 73%)! See some of our favorite quotes from the patient and her family below.
  
  • “This is the thing that allows mommies to sleep through the night.”
  • “It’s really exciting … it keeps my sugar at a steady level.”
  • “With type 1 diabetes, you’re making decisions about your blood sugar minute by minute … that’s a huge burden especially on a kid … this new pump frees up a lot of brain space to think about the kinds of things a kid should be thinking about.”

Standardized Glucose Reporting: The New EKG for Diabetes (Sponsored by Abbott and Dexcom)

We’ve gotten accustomed to attending conference symposia about the Ambulatory Glucose Profile (“the EKG of diabetes”) that are sponsored by Abbott, but at AADE, for the first time to our knowledge, Abbott and Dexcom CO-SPONSORED the session! We take this as another sign of positive momentum for AGP adoption in clinical practice, just two months after Dexcom added the standardized report to Clarity. Pressure for widespread adoption is mounting from the diabetes research and clinical communities, who agreed last month at the Outcomes Beyond A1c meeting that AGP is the way to go for displaying data. Abbott, Glooko (Diasend), Roche, and Dexcom have all taken the step. In his talk, Dr. Rich Bergenstal pointed out that even though the likes of Tidepool and Medtronic haven’t officially licensed AGP, their reports (on Blip and CareLink, respectively) look an awful lot like the modal day report – we’ve heard this from others and are very glad to see movement toward one standardized report. In our view, the sooner all players get on the same page, the better – we hope to see the day where all CGM manufacturers pitch in to co-sponsor the session.

• Dr. Bergenstal gave an excellent talk on the “journey from A1c to shared decision making,” comparing the process to a slinky falling down the stairs (the analogy makes sense given the slide design, below). Ultimately, it’s about sharing glucose data with patient in a user-friendly format (AGP) to make shared decisions. A1c is a good starting point – but a three-month average is not enough. We need actual glucose values to assess a person’s diabetes. He pointed to data from his just-published Diabetes Care paper, “The Fallacy of Average,” which indicated that an average blood glucose of 183 mg/dl could correspond to a 7%, 8%, or 9% A1c – “that’s not a real good metric. Instead of hoping you fall on the average of the average line, why not just look at the blood glucose.” Even then, he asserted that sporadic glucose (from SMBG) is not enough, but rather we need CGM. According to blood glucose check frequency vs. A1c curves from Miller et al. 2013 and Abbott, higher frequency of blood glucose monitoring leads to better glycemic control, so, he reasoned, CGM should confer even greater improvements. But CGM is not enough, because the field needs to align on standard metrics and how to display them [we’re there, at least on hypoglycemia (<54, <70 mg/dl), time-in-range (70-180 mg/dl), hyperglycemia (>180, >250 mg/dl), and variability (CV)]!). And finally, once everything is standard, clinicians and educators need to talk to patients and figure out appropriate paths forward. This talk was an excellent reminder of all the progress that has been made since the 1980s!

Non-FDA Approved Activity Related to RT-CGM Use Identified Through Photo Surveillance

Michelle Litchman, PhD (University of Utah, Salt Lake City, UT)

University of Utah’s Dr. Michelle Litchman explained how she used “photosurveillance” to analyze “#Dexcom” hashtags on Instagram for evidence of alternate site CGM wear. Among 2923 photos that were hand searched, 353 photos that meet the following criteria were selected for further analysis: depicted the Dexcom sensor on a body, the initial post was written in English, and the post was not an advertisement. Her team found that 64% of photos with CGM were not worn on the abdomen, the only FDA-approved site! Alternative sites were: the back of the arm (39%), thigh (12.7%), the forearm, back, front of the arm (3% each), the calf (2%) (!), the buttocks (0.6%), and other (10%; we’d love to know what creative sites people had come up with here). Notably, the photos depicting alternate site wear generated much more “buzz” than did abdomen wear, evidenced by three-times as many as likes and four-times as many comments. [Because of the small sample size, the p-values didn’t reach significance for either metric, but there appears to be at least be a signal.] Dr. Litchman’s group then looked at the valence of the comments on the photos: Most conversations took place under the photos of the abdomen, arm, and the thigh. While “success rates” were highest on the back of the arm, abdomen, and thigh, complaints of inaccuracy were highest on the abdomen (fascinating, but perhaps because due to a larger population use of this FDA-approved site, and therefore, more likelihood for a negative experience to come up), calf, and back. The only complaints of pain came from abdomen wear, and excessive bleeding complaints were most concentrated in thigh wear. This study is obviously not perfect – Instagram users are a self-selecting crowd (young, tech-savvy), those who use alternate sites may be more likely to tell the world about it, people with bad experiences with a given site may be more likely to comment on someone else’s photo, etc. – but it is definitely a cool use of social media to take a high-level look at what patients are doing in the wild (population health!). We also love the value this could offer companies, noting how clever patients are using their products and then using that to inform innovation, education, new indications, etc. (BCG’s Mr. Chris Bergstrom noted this in his Sunday keynote.) As Dr. Litchman concluded, “The viral nature of social media will likely expose individuals to non-FDA approved CGM activity. Social media is here to stay…The role of the CDE is to start having conversations with people. We can’t claim this site wear is safe. But it needs to be studied more in depth. Patients need more solutions. As an educator, it’s important to ask about real life. For me, the biggest thing is accuracy. If it’s working, I off-label support patients that wear CGM on their arm or wherever.” We absolutely love this cutting-edge work. We also noticed lots of CGMs worn on the upper arm at Friends for Life this year – see that highlight here. We wonder if the next-gen of sensors will pursue this wear location, including Dexcom’s G6 (FDA submission in 3Q17).  

• Dr. Litchman and her team also briefly looked at how long patients who talked about it on Instagram were wearing CGM. Among 40 patients wearing their CGM for greater than seven days, ~20% wore for 8-14 days, ~10% wore for 15-21 days – one even wore for 38 days! This data has long been known – patients extend sensor wear well past the approved length – though it does raise tough decisions on driving CGM sales vs. remembering patients’ needs. Many extend wear time due to cost, which is obviously critical and translates into fewer sensors purchased overall. How should companies weigh this balance? We wonder if Dexcom and Medtronic will ultimately build in auto-shutoff at some point, similar to FreeStyle Libre – perhaps this will happen when/if both companies move to entirely disposable systems. At that point, the cost may also be low enough that extended wear time will be less of a patient need.

The Next Generation Omnipod Systems

Trang Ly, PhD (Insulet, Billerica, MA)

Insulet VP/Medical Director Dr. Trang Ly reviewed the Omnipod Horizon Automated Glucose Control System, similar to the deep dive at ADA. Her remarks initially implied (to us) a push back in the development timing (by ~1 year), though Insulet has since confirmed in an email message to us that the last update in 1Q17 is still on track – a “2019” launch, a “2018” pivotal study, and “2017” pre-pivotals. The company did emphasize that additional time might be needed, given unpredictability in regulatory and the potential for a limited market release – of course, that’s true for any company and we’d assume that unpredictability is reflected in the remarks on expectations. This did not come up on the 2Q17 call last week; we’ve included a table below with links to recent coverage, just to be clear about what timelines have been publicly reported. Insulet is certainly cruising right along on studies and many might believe that a pivotal/submission delay would be surprising, given very rapid study progress to date, although we have certainly seen complexity arise with competitors working on the closed loop (other companies have experienced delays as reviewed below so it’s not unheard of – we certainly want all the companies to get the submissions right). Dr. Ly and her team have already overseen a number of feasibility studies (see our ADA coverage for a summary table), now in 92 patients, amounting to 4,584 hours of closed loop and 120 nights (up 10 additional patients, >1,000 hours, and 50 nights since ADA!). A five-day hotel study (n=48), the third IDE study, is ongoing at three centers and should wrap up in October. Developing and launching an automated insulin delivery system is an enormous undertaking, and pegging a firm launch date at this point is obviously impossible – we think a “limited market release,” if Insulet considers one, would be smart and would pull a page out of many other product introductions over time, most recently the 670G playbook. Medtronic cruised through pivotal completion, submission, and approval last year, though the 670G has only rolled out to ~1,000 people (as of Keystone) – getting things up and running post-approval certainly takes a lot of time and delicate care. Meanwhile, Insulet’s competitors do continue to push back pivotal and launch timing: Tandem’s PLGS back one quarter (summer 2018 launch), Beta Bionics insulin-only back 9-12 months (2H18 pivotal), Bigfoot’s pivotal back ~1 year (2018). Who will be second to market in the US? Who will have a truly differentiated product that expands the market? We’re glad to see Insulet pushing hard and have no question the company is ultra-committed to getting a product to market. This is fantastic to see since it was only a few years back that Insulet management was downplaying the closed loop and saying it would “never” happen in their lifetimes!

• A phase 3 study of the Lilly U500 Omnipod PDM in type 2 patients (VIVID; n=416, primary outcome: Change in A1c at 26 weeks) just completed with “really exciting data” and Dr. Ly hopes it will be presented at ADA 2018 in Orlando. Meanwhile, a safety study of the U200 version will start “soon” (expected to begin in early 2018, we last heard). Based on this month’s financial update, U500 is expected to launch in 2019, followed by a 2020 launch of the U200 PDM. Both of these devices promise to open up a much larger swath of the diabetes market, catering to those with higher insulin requirements. We’ve been hearing the promise of U500 for years and years and look forward to seeing this finally move forward.
• Insulet is “almost at the end of human factors” testing with the new Bluetooth-enabled Omnipod Dash PDM (locked down Android phone) and pod. The system debuted at ADA and is on track to be submitted to FDA in 4Q17, which we think could enable an early 2018 launch, assuming a rapid review. See our detailed coverage of Dash from the ADA booth and Insulet’s product theater – we think the product looks terrific. Dr. Ly stressed the Wi-Fi connectivity (new news, as there is no cellular), hopefully enabling auto-upload of data to the cloud and remote monitoring when a nearby smartphone isn’t around (this is our speculation). Insulet also has a follow app for parents/caregivers that will simultaneously launch with Dash. This will make such a huge difference for patients and families, particularly families of children.

Insulet Horizon Timing

Closer Look Report	Horizon Timing Shared
Insulet 2Q17	No pivotal or launch timing shared. Entering third IDE study (n=48 hotel).
ADA 2017	Pivotal trial in “2018”
Insulet 1Q17	Launch in “2019” Pivotal trial in “2018” Pre-pivotals in “2017”
Insulet 4Q16	Launch in “late 2019”
Insulet Investor Day	Launch in “late 2019” Pivotal trials in late 2018-early 2019

• Dr. Ly noted that Insulet continues to lobby for Omnipod to be covered by CMS. Said Dr. Ly, “this is our number one priority, and our CEO is on it.” Management has been talking about this priority for quite some time. Most recently in May, Mr. Sullivan said that he has “every confidence we will get Medicare coverage … hopefully soon.” Per that update, discussions focused on whether the OmniPod should fit into Part B or Part D. This was not mentioned in the call last week. We hope Insulet can learn from Dexcom’s G5 playbook on this one! Dexcom estimated in 1Q17 that Medicare covers ~300,000 type 1s in the US (~20% of the market) and ~500,000 type 2 intensive insulin users (~33% of the market). As a side note, we heard FDA leadership at the recent “Glycemic Outcomes Beyond A1C” assure the audience that Medicare coverage for Insulet’s Omnipod was a priority in Washington DC; even though FDA does not control these coverage decisions, this was great to hear.

Connected Health and Digital Connections: A Look into the Future

Ellie Strock (Voluntis, Minneapolis, MN), Rita Saltiel-Berzin (BD, New York, NY), Paul Lasiuk (Healthy Interactions, Chicago, IL)

A panel of experts discussed the progress in diabetes management made possible by technology, expressing excitement for the role educators will play in shaping the future of digital health. Given their in-depth experience troubleshooting diabetes therapies, BD’s Ms. Rita Saltiel-Berzin noted the potential educators have to be instigators of change in the technology landscape, noting that some team members “have no idea what kinds of questions to ask” when designing digital health solutions. Since questions often arise in real-time, it will be critical to understand what patients ask and to help them tackle teachable moments – these almost never occur in the presence of providers. While there is certainly a lot to be excited about (Voluntis’ Ms. Ellie Strock pointed to the freshly-announced FDA pre-certification process for app clearance), there is still much to be accomplished. Mr. Paul Lasiuk, CEO and co-Founder of Healthy Interactions, outlined four key reasons why, despite his estimate that ~$8 billion has been invested in digital health this year, a large chunk of the capital most likely won’t prove fruitful: (i) There’s a massive disconnect between consumer and healthcare use – getting people to be active in their healthcare management has not translated very well, thanks in part to a systemic culture of viewing clinicians as responsible for fixing problems; (ii) The most common diabetes demographic, that of a slightly older population, views the smartphone strictly as a phone and not a device with wide-ranging uses; (iii) In a space occupied by 165,000 apps (of which more than 1,100 are diabetes-related), the digital health world is a crowded, confusing place with ambiguous regulation; and (iv) Reimbursement issues are a major barrier. For all of these reasons, Mr. Lasiuk cautioned that digital technology is not a silver bullet, and easing of patient burden must be emphasized. These were fair criticisms, though we must remember the field is at a nascent stage and still laying important groundwork now for future scale. As WellDoc’s Vice President for Clinical Advocacy Malinda Peeples pointed out, Welldoc has been able to effectively translate their products for real-world use and have seen excellent senior engagement in their technology; in fact, those over 60 years-old are some of their most active users! Dr. Deborah Greenwood echoed Mr. Lasiuk, pushing for simplicity. She recalled a poignant statistic indicating that if people with diabetes did everything providers asked of them, they would need to allot 2.5 hours/day to their self-care – insane, especially because today’s technology hopes to diminish burden. We agree that patients, CDEs, and others on the front line will absolutely need to be the first consulted as manufacturers approach digital health, as only they can comprehend the lived experience of diabetes and how an intervention would fit in and add value.

• One of the most common clinician/educator fears is whether technology will one day replace in-person healthcare – when prompted with this question, the panel responded with a resounding no. Onduo’s Paula Leclair noted that, as technology evolves, so will the job of the diabetes educator, especially as lifestyle coaches become more integrated (much like the industrial revolution created many new jobs and changed the jobs of farmers, but didn’t necessarily put them out of work). Still, as Ms. Saltiel-Berzin pointed out, the in-person aspect is critical for accountability – a patient may not feel as accountable to Alexa or Siri or an app as much as a real person. (Of course, incentives, joyful experiences that make life better, and smart remote monitoring might change this.) Furthermore, as per Ms. LeClair, Siri is not exactly whom she would want to talk to if in DKA. Instead, she views technology as an adjunct that is part of the patient-provider relationship. Mr. Lasiuk agreed, defining human interaction as the cornerstone of care, with technology as a facilitating toolkit.   

Questions and Answers

Q: How are we going to pay for this? How will our insurers and Medicare pay for educators to see patients in the digital scene?

Dr. Greenwood: I was really disappointed to see Medicare not cover the digital DPP. I thought this would be our breakthrough. Supposedly they will cover digital make-up classes but that was a huge blow and I was expecting they would cover it.

It’s Time to Rethink Professional CGM: The New FreeStyle Libre Pro System (Sponsored by Abbott)

Etie Moghissi, MD (Marina Diabetes and Endocrinology Center, Marina Del Rey, CA)

In an Abbott-sponsored symposium, Dr. Etie Moghissi (Marina Diabetes and Endocrinology Center) shared a rave review of FreeStyle Libre Pro (“this has truly revolutionized the way we look at patient’s data retrospectively”), attempting to address concerns of inaccuracy in hypoglycemia and offering her high-level thoughts on blinded CGM. Midway through her talk, Dr. Moghissi invited the audience to revisit the “important” FDA label notice on hypoglycemia inaccuracy: “The device may inaccurately indicate hypoglycemia. The results of the clinical study conducted for this device showed that 40% of the time when the device indicated that user sensor glucose values were at or below 60 mg/dl, user glucose values were actually in the range of 81-160 mg/dl.” This label note (bottom left corner of page 4), according to Dr. Moghissi, refers to just 53 out of the 12,331 paired Libre Pro-YSI values collected in the accuracy study, equating to just ~0.4% of all of the data. We thought this was a very questionable argument – a concern about over-reporting hypoglycemia cannot be disregarded just because only a few study data points were in the hypoglycemia range. This fact is true for all CGM sensor accuracy studies, and for context, we’ve included the labels below from the Libre Pro, Dexcom G5, and Guardian Sensor 3. While comparing across studies perfectly is impossible, it does show Libre Pro is the most challenged in hypoglycemia and collected the fewest points in this range. For values 40-80 mg/dl, Libre Pro was within 15%/15 mg/dl for 53%-58% of the time vs. 89%-91% for Dexcom’s G5 vs. 77%-87% for Medtronic’s Guardian Sensor 3 (calibrated twice-daily). We’d also note the huge discrepancy of paired points in the 40-80 mg/dl relative to all study points – just 4% with Libre Pro vs. 14%-15% with G5 and 15% with Guardian Sensor 3. Abbott noted that the objective of the study was not to be a direct comparison, and if it was, it would’ve been designed differently to capture the performance of the device in hypoglycemia. Of course, Libre Pro is far, far better than what patients would get on fingersticks alone, and the device is used for trend/pattern recognition rather than real-time decision making. Though the real-time and professional FreeStyle Libre sensors are different products, we’ll be interested to see how hypoglycemia accuracy is characterized by FDA on the former’s label, once and if it is approved (under review for nearly a year). We note the views of many patients that the values with the real-time system are enormously helpful and take the value of CGM far beyond SMBG.

• Dr. Moghissi emphasized that not only has the system and its accompanying AGP revolutionized the way practice evaluates continuous glucose data, but it’s also changed her conception of who is a candidate for CGM: She has long thought all type 1s need personal CGM, and even if they refuse, FreeStyle Libre Pro can convince them something needs to be done. She also believes most type 2s need to use Libre Pro intermittently: “We have not had a user-friendly tool for type 2s who could benefit from CGM.” For this population, she staunchly argued against unblinded professional CGM – claiming that patients “see religion” and change their behavior during the week of wear because “they want to be good,” making it difficult to parse out behavioral and therapeutic effects. One thing’s for sure … clinicians seem to be over-the-moon with the ease, cost, and adaptability of this device.

FreeStyle Libre Pro Label (page 45)

Dexcom G5 Label (page 290)

Medtronic Guardian Sensor 3 FDA Summary (page 46)

Technology Works Best When it is Accurate

David Klonoff, MD (Mills-Peninsula Health Services, San Mateo, CA)

In the first public talk following recent results online, Dr. David Klonoff discussed the Diabetes Technology Society’s BGM Surveillance trial (n=1035). The large study found that only six of the 18 tested BGMs received the seal of approval. In his discussion, Dr. Klonoff cited our Closer Look coverage on the results, which discovered that a shocking ~62% of the Medicare mail order BGM market in 2016 was for devices that did not pass the study (read here for our deep dive into the data and methods). The six BGMs that passed were Ascensia’s Contour Next (formerly Bayer), Roche’s Accu-Chek Aviva Plus, Arkray’s Walmart ReliOn Confirm/Micro, Agamatrix’s CVS Advanced, Abbott’s FreeStyle Lite, and Roche’s Accu-Chek Smart View. Dr. Klonoff expressed high regard for these meters, viewing them as “excellent” for having passed the rigorous testing undertaken in the trial. See the bullet below for those that did not pass. Dr. Klonoff and team designed the protocol with an all-star group of leaders from various organizations, claiming that their combined expertise made it impossible for any one company to write the study’s methods off as unfair. It’s a good point, and we’d add that the program was funded by Abbott – though one Abbott meter passed (FreeStyle Lite), its other (Walmart ReliOn Ultima) did not, which bolsters credibility. Further, by buying meters off the shelves, the trial avoided any enhancement or cherry-picking that would limit representation. Dr. Klonoff noted this is the largest study of BGM performance ever reported and we’ll be interested to see where it goes from here. The data clearly reinforce concerns that many FDA-cleared meters are actually inaccurate in the real-world, but it’s unclear how the FDA will use these results; Dr. Courtney Lias was previously excited about this program as a post-market “signal” to inform investigations. We also wonder if the trial will be repeated, assuming there is funding and interest in that. Presumably it could expand to CGMs one day, especially given what seems like a growing number of random companies that appear with sensors in exhibit halls. 

• The remaining 12 BGMSs that did not make the >95% cut included Arkray’s Walmart ReliOn Prime, LifeScan’s OneTouch Verio and OneTouch Ultra2, Abbott’s Walmart ReliOn Ultima, Bayer’s Contour Classic, Prodigy’s Auto Code, Omnis Health’s Embrace, Nipro’s True Results and True Track, Biosense Medical’s SolusV2, Suncoast’s Adovcate Redi-Code+, and Philosys’ Gmate Smart. The latter three met compliance a grim 71%-76% of the time.
• Dr. Klonoff first had the idea for this study after performing a literature review published in 2015 in the Journal of Diabetes Science and Technology – work from Drs. Guido Freckmann and others found that testing meters post-clearance identified many concerning trends. For instance, in one study, only ~75% met ISO 2003 standards, and only ~48% were compliant with ISO 2013 standards. Considering that manufacturing companies run these studies, Dr. Klonoff and colleagues wondered if meters aren’t as accurate as companies say they are, or if performance declines once they get on the market.

Finding New Ways to Deliver DSMES to Cut Through the Clutter

Scott Johnson (mySugr, San Diego, CA), Neal Kaufman, MD (Canary Health, Los Angeles, CA), Jennifer Schneider, MD (Livongo, San Francisco, CA)

mySugr’s Mr. Scott Johnson (a newly-minted grandfather!), Canary Health CMO Dr. Neal Kaufman, and Livongo CMO Dr. Jennifer Schneider comprised a lively interactive panel on the pros/cons of digital health, program recruitment, engagement, and analytics. During the discussion, the panelists were in full agreement that the pros of digital health are clearly scale and the delivery of the right information at the right time, while the main con is relationship development – as Mr. Johnson said, it can take a little longer to find the rhythm in a digital patient-clinician relationship, but companies are finding ways to overcome that. In their introductions, Dr. Schneider announced that Livongo now has almost 50,000 active users, up from 35,000 in May – the company will need a very big five months to more than double its user base and hit the goal of 100,000 by the end of 2017. Meanwhile, Mr. Johnson added that mySugr is currently in discussions with additional insurance companies worldwide to get the “mySugr bundle” (app, unlimited supplies, coaching, population management) covered, as it is in Germany by a large payer.

• On recruitment and engagement, Dr. Kaufman emphasized the power of data – “the more you know about your population, the better.” One of the strengths in the digital world, Mr. Johnson corroborated, is that it allows rapid trial, experimentation, and sequential iteration, until sweet spots reveal themselves: “It’s a lot easier to do this digitally at a scale. Imagine trying to do that with a paper mail campaign.” Dr. Schneider talked about how Livongo can, for example, develop 100 ways to talk about nutrition to women in the Northeast, and figure out which is the most engaging for whom. She added that, in terms of engagement, we shouldn’t think inside the box for diabetes digital health technologies, but rather look at other, delightful consumer technologies for inspiration.
• Notably, both Livongo (10 active data scientists) and mySugr are expanding their data science team to look into patterns and trends in efforts to generate insights and, especially in the case of Livongo, prevent glycemic excursions instead of solely reacting to them – we love the idea of predictive analytics, assuming they are accurate (not false alarms) and patients don’t get fatigued by alerts. mySugr head of R&D Mr. Fredrik Debong apparently sifted through 40,000 (de-identified) pizza boluses (!) from mySugr users to try to figure out the optimal timing for a bolus for himself – Mr. Johnson didn’t reveal the outcome of this study, but it was yet another reminder of the treasure trove that exists and can hopefully leveraged in the years to come. Dr. Kaufman stressed the importance of taking information about patients and using it to reach people at an emotional level such as through the use of authentic stories during all aspects of an intervention … from outreach, activation, sign-up, show-up, to participate and succeed. 
• Drs. Kaufman and Schneider expressed optimism for the future of value based care, even though very few government payers cover digital interventions today. CMS declined to make a decision on reimbursement of virtual DPP programs in November and will revisit the issue this year – the delay is disappointing though it could be worse. Dr. Schneider indicated that Livongo is already working with some payers in a value-based framework (wed note one of its investors is Humana), and Dr. Kaufman emphasized that “as you get further and further into value-based care, if you can demonstrate the ability to recruit people and succeed, then you can get paid for that service.” We are glad to hear this. “Value-based healthcare” has definitely becoming a buzzword over the last year, and we look forward to more specifics on what these deals look like – what are the outcomes that are tracked, what’s the time period, what’s the payment structure, what are the shared savings and incentives, etc.  At the end of the day, “improving outcomes from any behavior change intervention or self-management support program – in-person or digital – should be based on programs which have been proven to work to get outcomes that matter for the specific targeted population,” said Dr. Kaufman. “This is particularly important when digital technology is used to translate a validated in-person program to one being delivered digitally.”
• How should digital coaching build the basic diabetes self-management education skills? A questioner astutely pointed out that it sounds like most digital coaching aims to “put out fires” (address very high or low blood glucose values), and is often underutilized in building a basic skill set. There’s a gap, she continued, in the time that a person is diagnosed with diabetes and given a BGM, and their first in-patient CDE appointment. This subject clearly resonated with Mr. Johnson, who plainly stated that “right now, we’re still learning what works best at mySugr … Could you imagine learning you have diabetes and being given a meter, then going to face your first meal? Just think about that for a second. Wow, right? There’s a gap there. We’re still learning how to address that.” As usual, we appreciated his candor and insights. Ms. Tobi Smithson, a Livongo CDE (and the panel moderator), suggested rather that remote education fills the gap, allowing newly-diagnosed people to check in as many times as needed.

The Use of Continuous Glucose Monitoring with Multiple Daily Injections of Insulin in T1D and T2D: The DIAMOND Study

Rich Bergenstal, MD (International Diabetes Center, Saint Louis Park, MN), Laura Young, MD, PhD (UNC, Chapel Hill, NC)

IDC’s Dr. Rich Bergenstal overviewed data from Dexcom’s DIaMonD study of CGM in type 1s on MDI, type 1s on MDI switching over to pump (published last month in Lancet D&E), and type 2s on MDI (publication coming), echoing commentary from others such as Drs. Roy Beck and Bruce Buckingham. We were glad to hear that the pump crossover phase data is now published, following the ATTD poster presentation. Dr. Bergenstal noted that the study design was “pretty standard care-feeling,” setting it apart from other CGM studies that entailed significantly more outreach from clinicians. The investigators definitely made a big deal out of this fact in the original ADA 2016 DiaMonD presentation too. Like Drs. Buckingham and Beck at Keystone last month, Dr. Bergenstal underscored the high CGM wear time in both type 1s and type 2s. He also highlighted, based on data collected by Dr. Bill Polonsky, the improvements in diabetes-related quality of life obtained from wearing a sensor – “they didn’t see an improvement in overall well-being, but if people feel better about their comfort with diabetes, that’s a pretty big part of their life.” The pump extension phase in type 1s, showed that patients see a lot of benefit with CGM, and adding a pump prompts a solid time-in-range benefit on top of that (+83 minutes/day, adjusted mean difference). Dr. Bergenstal noted that the pump group saw slightly more hypoglycemia <70 mg/dl) (+15 minutes per day), while the MDI group had slightly less hypoglycemia (-9 minutes per day; p<0.001). The difference in A1c was not statistically significant: the pump group saw a +0.3% change in A1c vs. +0.1% in the MDI group (baseline: 7.6%; p=0.32). Dr. Bergenstal leaves it up to the patient and provider to perform the risk:benefit calculation. He included his always-persuasive calls for outcomes beyond A1c (specifically time-in-range) and the Ambulatory Glucose Profile (AGP) for viewing data. Dr. Bergenstal concluded that “it’s time we thought about offering options to patients. The time has come, and this is an important issue. The time is even more here now that there is a therapeutic indication, a major breakthrough.”

• After an educator complained that patient appeals for therapeutic CGM were being denied by Medicare, a Dexcom rep noted that the company has shipped “over 100” G5s to Medicare beneficiaries thus far. “If they get denied,” she added, “it’s primarily because of chart notes.” We learned on the 2Q17 call that Dexcom began shipping the first few “test case” G5 Medicare bundles in the last two weeks of July – the numbers wasn’t specified, but the implication was not many had been shipped. Assuming these claims are adjudicated and actually paid, shipments will roll out more aggressively in 2H17. There are now 20,000+ Medicare patients in the pipeline, more than doubling the 10,000+ as of 1Q17. We’re not surprised at all by the low number of shipped bundles at this point, given the crazy process and sometimes mind-boggling decisions of CMS. We also hope to see more movement on getting access to “Share” for those working on the Medicare approvals – this will take some time, as we understand it.

UNC’s Dr. Laura Young stated that due to the results of  the Monitor Trial of SMBG in non-insulin-treated type 2s (ADA poster; JAMA Internal Medicine), for which she was a PI, she has started telling some patients not to check glucose. “They don’t really like it. Encourage shared decision making. Low risk patients on orals probably don’t need to test. You can take that burden off.” The results did show that performing a fingerstick once per day doesn’t improve glycemia, nor health-related quality of life (HRQOL) (see more detailed results below). Her commentary is unfortunate to hear, since it should bring up more questions rather than putting the issue to bed. Indeed, we’d note that findings from the SMBG Study contradict those from Monitor (both were presented at ADA). In that trial, random assignment to a group that performed structured SMBG resulted in an early and sustained ~1% A1c drop vs. assignment to a group that did not check glucose. Notably, the baseline A1cs were slightly higher in the SMBG Study (~8.5%), but we’re not sure what the “structured SMBG” looked like in terms of how many times per day and when the enrolled patients were encouraged to check. These conflicting studies add to this controversial area, and we’ll be fascinated to see what is possible once low-cost real-time CGM is applied to this group. We wonder if the real problem for the Monitor Trial was that the patients weren’t getting enough of the right kind of data at the right time – paired, more frequent, and structured or via real-time CGM! We also wonder if professional CGM dosed at certain times – at diagnosis, when changing treatment – would be a solution too. We’re not ready to give up on the value of glucose monitoring in non-insulin users, especially because food and exercise choices are SO relevant, and CGM can help illuminate them in a way SMBG cannot. Dr. Young noted that the rationale for the once/day checking was because that’s what Medicare pays for – this does show that value of more frequent/expensive technology will need to be proven.

• After 52 weeks of no SMBG, once-daily SMBG, and once-daily SMBG + automatic tailored messages delivered via the meter in the Monitor Trial, the group with no SMBG had experienced a 0.04% increase in A1c (baseline 7.52%), the once-daily SMBG group had experienced a -0.05% A1c drop, and the one-daily SMBG + messaging group had experienced a 0.10% drop in A1c. None of these changes were statistically or clinically significant (p=0.74). HRQOL, as measured by the “physical” and “mental” arms of the SF-36 survey, was also unchanged over the span of a year. Dr. Young said that her “bubble was really burst” by this negative finding, since it took three years of her life, but she’s come to accept the outcome. It naturally goes without saying that we’d love to see how “time in zone” changed since we don’t see A1c as the “be-all, end-all.”

Real World Experience with the Hybrid Closed-Loop Insulin Delivery System

Shannon Beasley (IDC, St. Louis Park, MN) Beth Olson (IDC, St. Louis Park, MN)

IDC’s Ms. Shannon Beasley and Ms. Beth Olson detailed useful tricks for educators with patients on the MiniMed 670G, discussing expectation management, workload, and device optimization. Ms. Beasley observed that the 670G has brought substantial mental relief for patients and their families, commenting, “This is the big deal. A1c is great, but quality of life is really where we want to go with a lot of people.” Despite the evident glycemic benefits, both educators had plenty of tips and cautionary notes that educators should be aware of – well worth the read!

• To help patients stay in auto mode as much of the time as possible, Ms. Beasley recommended having them enter auto mode early in the day in preparation for extra calibrations requested by the system. When the system first starts up, she noted, it requires more user interaction. By starting in the morning, the operator avoids having to calibrate multiple times late at night. Ms. Beasley advised telling patients to expect even more than 3-4 calibrations per day – better to disappoint them initially rather than leave them frustrated with the device. Similarly, Ms. Olson recommended that educators inform their patients to expect a post-meal rise and emphasized responding to alerts and alarms. She also cautioned that patients may have a difficult time adjusting to gradual glucose corrections (“soft landings”), but stressed the importance of trusting the system. We’ll be interested to see if overcorrecting (stacking a bolus on top of increased basal) is a concern, particularly in an early adopter population.
• Ms. Beasley said she believes the 670G will demand additional work from diabetes educators. While acknowledging the efforts of physicians, Ms. Beasley noted that educators are the ones “in the trenches,” tasked with duties clinicians may not necessarily address. In particular, Ms. Beasley admitted that the data reports are incredibly different and can be confusing and time-consuming to analyze. Still, she remained optimistic: “We’ll get used to it, but in the beginning, it will take more work.” When faced with reading a CareLink report, Ms. Beasley advised educators to focus on why a patient gets kicked out of auto mode, which she claimed guides her discussions with patients.
  
  • Ms. Olsen suggested that educators assess CareLink reports in a series of seven steps: (i) evaluate the glucose profile for hypoglycemia, hyperglycemia, and glycemic variability, (ii) review time-in-range, (iii) review the statistics panel for time in auto-mode and sensor usage, (iv) analyze auto-mode exits, (v) review bolus and basal patterns, (vi) review auto basal rates, and (vii) note any changes, use of temp targets, etc. Ultimately, the promise of automated insulin delivery is to jettison data analysis like this; obviously since the 670G is a first-generation product, this will be still be needed. 
• Ms. Beasley said educators may need to think differently about pumps. The 50:50 ratio rule for basal:bolus may not apply to the 670G. Instead, Ms. Beasley believes 30:70 (less basal, more bolus) may be more appropriate. We heard the same from Dr. Rich Bergenstal at Endo – patients can cover meals better than they used to, and the system will shut off basal delivery on the back end as needed. We’d emphasize that these ratios are highly carb dependent – for those eating fewer carbohydrates, the ratio could easily be reversed.
  
  • On Loop over the past 31 days, Adam has been at 82% basal and 18% bolus insulin, and has seen solid outcomes: a mean glucose of 112 mg/dl (SD: 24) and 88% time in 70-140 mg/dl – and he does forget to bolus sometimes for low-carb meals on Loop! (His target is set at 90-110 mg/dl, and the pump is allowed to give 5x his normal basal rate – obviously more aggressive than the 670G.) Still, we’re skeptical of “ideal” basal-bolus ratios, especially striving for patients to “hit” a certain ratio. If mean glucose is acceptable with high time-in-range and low hypoglycemia, does the ratio really matter? As more insulin gets shifted into basal, it actually translates into less manual (bolus) insulin dosing burden for patients – a good thing.
  • Ms. Beasley noted that the pump algorithm learns a patient’s individual insulin needs over time and is constantly updating, so the “let it drip while showering/swimming” philosophy could actually be dangerous. Therefore, suspending the pump when it is not attached is imperative – this is a great point and one we have not heard before. This also applies to manual injections, should any be taken – the system won’t know there’s extra insulin on board and would therefore assume that the patient is more insulin-sensitive than he/she really is. We don’t see this as a huge issue, since it’s unlikely someone would both be wearing a pump and taking insulin injections.
• When determining whether a patient is suited for a hybrid closed loop system, Ms. Beasley recommended several general considerations: (i) ability to respond to alarms; (ii) comfort level troubleshooting; (iii) carb counting skill (which Ms. Beasley believes especially critical!); (iv) willingness to learn a new system; (v) tendency to bolus before eating; and (v) prior pump and CGM use. At IDC, the 670G was only extended to experienced pumpers, although Ms. Beasley acknowledged that it is possible for a MDI user to learn the system – it may even be easier, as they might be more likely to approach 670G with a hands-off, “let it work” approach.
  
  • We do not believe automated insulin delivery will live up to its promise if these consideration need to be hit. Systems ultimately should reduce or eliminate all of these steps, giving patients much better outcomes and more leeway to make mistakes.
• Ms. Beasley admitted that the 670G is by no means a perfect system. Patients reported that the new device is heavier and more difficult to wear (earlier Medtronic pumps were easy to read while attached to the waist band, but the 670G has to be taken off because it is vertical). Further, one patient dropped out of the pivotal study because she felt the system was not as responsive to her highs as she could be on her own – this aligns with BDC’s Ms. Laurel Messer’s point at CDTM that the system is not for the “type A+s” (super engaged) or “type Zs” (not engaged). Perhaps most importantly, there is no sharing feature, although Ms. Beasley noted that there are “rumblings” sharing will return in a later iteration of the product. Medtronic’s Dr. Fran Kaufman shared at Keystone that a 670G with connectivity is coming, though there is no timeline to report.
• The temporary glycemic target of 150 mg/dl, intended for exercise, has been somewhat underutilized – Ms. Beasley acknowledged that the pivotal trial cohort did not find much value to it. Indeed, Medtronic Diabetes CMO Dr. Fran Kaufman shared at Keystone that patients are only using the temp target ~2% of the time (~50 minutes per day, assuming everyone is using it equally). However, she sees potential in the feature, as did one patient highlighted in the presentation (see further below for our favorite quotes from patient-perspective videos).
• Quotable quotes from video interviews of IDC patients on the 670G:
  
  • “If you think, ‘I won’t have to do anything,’ that’s unrealistic. I’m doing more blood sugar testing now than I did before, but it has improved my blood sugar and A1c.”
  • “For me what’s been huge is maintaining stable glucose levels throughout a flurry of activity.”
  • “I think about my diabetes less. I think about it a lot because it’s part of me and who I am and a part of everything I do. But if I have to go into a meeting or drive somewhere, I don’t think about it the same way anymore. I’m more relaxed about those things.”
  • “My mom really likes it. She doesn’t have to wake up in middle of the night anymore or worry about me not having good blood glucose. It allows for a much better night’s sleep.”
  • “I do use the temp target a lot. It’s not entirely effective for rigorous exercise – if you’re doing really heavy cardio it won’t work so well. But what it really works well for is walking 18 holes for golf. It’s getting you up there and keeping you up there. Before using the 670G, I’d just be chasing lows the whole time.”

Questions & Answers

Q: In pediatrics, I have grave concerns. Are there issues with teens? How much teaching did you provide? How much training for school nurses?

Ms. Beasley: We provided no training for school nurses. I have reservations about putting a seven or eight year-old on it. They won’t comprehend “why am I on white shield mode, how do I get back in?” There’s a learning curve. What do we need to do? Do we teach school nurses? It’s on the kid and family. We don’t want to put more on the nurses. How much is too much? [Theoretically, data from the 7-13 year-old study, which will be read out soon, should address these concerns – Dr. Kaufman noted at Keystone that in a total of 16,200 patient-days (36 patient-years), the safety profile is equivalent to that seen in previous studies.]

Ms. Olsen: A couple of teens go to camp, hockey, college, and their A1cs are 5.9 to 7.5 for two years. It can be done and done safely. 

Population Health Diabetes Education: Leveraging Digital Health and Patient Generated Health Data (PGHD)

Janice MacLeod (WellDoc, Baltimore, MA), Malinda Peeples (WellDoc, Baltimore, MA)

Ms. Janice MacLeod and Ms. Malinda Peeples, a dynamic educator duo from WellDoc, provided insight on how diabetes educators can take part in leveraging digital health to improve outcomes on a public health level. For Ms. Peeples, educators can choose one of three options: (i) “stick to your knitting” (we all need sweaters, but technology has already introduced incremental change); (ii) “get out of the sandbox” (she applauded AADE for looking beyond diabetes for technology applications); or (iii) “change the game” (urging educators to push the envelope and practice at the top of their licenses). Ms. Peeples emphasized that educators can help answer critical questions, but in order to do this, the idea of serving one patient at a time must be refreshed to include a broader view – population health, risk stratification, etc. In her own words, “the data is there,” yet it often feels like the community is ignoring or underutilizing it. As an example, Ms. Peeples questioned why programs are still being built given concerningly low participation – clearly, a new solution is needed. Ms. MacLeod detailed the importance of meaningful data interpretation, noting that results are simply numbers unless they are used to forge meaningful partnerships with patients, incorporating productive interactions, two-way communication, and actionable advice. Educators of the future will have to envision a new framework involving a complete feedback loop, translating patient-generated data to enhance health management. Excitingly, when Ms. MacLeod asked audience members whether they worked in a practice with some form of “virtual touchpoint” between in-person visits, the majority of the room raised their hands. (If this is a remote monitoring via connected devices and messaging, we’d be psyched! Of course, this might just be EMR email alerts, which wouldn’t be saying too much.)

• Ms. MacLeod discussed several features of WellDoc’s BlueStar app to exemplify how data can be used meaningfully. One of the most critical aspects of BlueStar, she said, is that it provides patient support while also keeping the patient connected to an in-person team of providers. WellDoc prides itself on providing the right information at the right time, responding to what patients are entering and need in the moment – an aspect both Ms. MacLeod and Ms. Peeples stressed as important in driving engagement.
  
  • Ms. MacLeod highlighted how BlueStar’s sharing feature can help providers extend their reach, effectiveness, and efficiency, allowing insight into data on a consistent basis. In particular, Ms. MacLeod finds that she can better monitor patients’ self-management, engagement, and barrier resolution, which guides her conversations with her patients in-person. Even small details like being able to ensure that patients have sufficient prescriptions for strips and lancets can be impactful.
  • For Ms. Peeples, the defining aspect of WellDoc is that it was not developed in a prescriptive manner. Rather, WellDoc observed actual physician offices, noting what diabetes education programs were already doing in the real world. WellDoc’s BlueStar is the result of the collective learning that ensued.
• Ms. Peeples detailed the importance of keeping technology simple, emphasizing initial engagement, patient identification, enrollment strategy, onboarding, and configuration. When it comes to identifying patients most likely to benefit from digital health tools, she cautioned educators to avoid common misconceptions that technology is only for young people – in fact, WellDoc’s most active users are 60 years and older! Ms. MacLeod advised that when choosing a tool, the educator narrow down the plethora of options by looking at those with evidence-based outcomes.
• Both speakers recommended assigning a digital champion to monitor technology use in a clinic. This person is responsible for ensuring that technology is used meaningfully across a practice and could be a health coach, care coordinator or diabetes educator. We like this idea!

How Can Diabetes Educators Harness the Potential of Digital Health?

Kevin Clauson (Lipscomb University, Nashville, TN)

Lipscomb University’s Dr. Kevin Clauson discussed several digital health tools he feels will enhance diabetes and self-care management, separating them into three buckets: (i) lifestyle, (ii) adherence, and (iii) disease-specific. He also identified the key drivers of digital health development to be social media, participatory medicine (patients as partners work better than a paternal system), cost and ubiquity of devices, cost and availability of data, and an interdisciplinary team working together to produce outcomes. Mr. Clauson wrapped up his discussion by posing a question to the audience, one that all thought leaders might do well to consider: As we move forward, how will patient data be extracted, and how does this impact workflow? Will we implement a model similar to that introduced by Apple Health, in which data is aggregated from different sources (apps) and transmitted to Epic for analysis and communication? Complicating the matter further is the number one concern Mr. Clauson gets from clinicians: “How liable am I with this data? I don’t have time to assess all these things.” This continues to be a concern and is clearly something that needs to be addressed with clinicians – perhaps through software user agreements, a clinic-patient contract, public policy, etc.

• When evaluating lifestyle technology, Mr. Clauson cautioned against writing off a particular device just because it appears to be low tech – these tools can still have a huge impact. Mr. Clauson was particularly excited about a next generation wearable due for release this summer, a sleek ring by Motiv which tracks heart rate, steps, sleep, and other physiological metrics. He also noted the importance of often-overlooked features when considering adherence to lifestyle tools. For example, every time someone removes their wearable to charge is an opportunity to not put it back on. Mr. Clauson mentioned the Misfit wearable (now owned by Fossil), which uses a traditional watch battery replaced every six months, as a step in the right direction. We agree – charging must get better. As great as the Apple Watch is, charging it daily is frustrating.
• Mr. Clauson featured Glooko, Livongo, One Drop, BlueStar, and Tidepool as particularly noteworthy disease-specific digital health tools. Mr. Clauson was impressed with Glooko’s currently-recruiting trial (n-=260), as well as its ability to be used in conjunction with EHR. He found BlueStar’s published data similarly remarkable, calling it “the most evidence I’ve seen supporting a platform.” Mr. Clauson noted Livongo’s display and emphasis on simplicity to be especially well-suited for an older demographic, and appreciated the on-demand access to CDEs. He was surprised to see the One Drop Chrome BGM kit in the Apple store, as he considered Apple to be moving away from promoting these types of products. (We disagree; if anything, Apple is moving more into digital health through iOS taking insulin doses, Native Core Bluetooth to send CGM straight to the watch, etc. The iBGStar was years ago!) Lastly, Mr. Clauson noted that by allowing for selective sharing with different providers, Tidepool puts the control into the hands of patients.
• With an eye towards the future, Mr. Clauson provided a brief overview of upcoming technology at the top of his watch list. He observed that progress on Google and Novartis’s rumored smart glucose-sensing lens has slowed down quite a bit (no public updates in ages), and several companies have begun catching up, with one unnamed group promoting virtual reality overlay. Virtual reality is a promising field itself, he said, with the potential to teach empathy, simulate hypoglycemia (see the exhibit hall!), and more. Mr. Clauson also detailed the Healthcoin, a software platform aimed at preventing diabetes by leveraging blockchain to provide monetary incentives. The website is cool though the jargon makes it confusing – we’re not quite sure what this actually entails.
• Mr. Clauson mentioned PillDrill, AdhereTech, Proteus Digital Health, and Care4Today as a few of his favorite adherence products and developers. PillDrill, released in January, is a smart vial scanned over a hub to log dose information, which can then be transmitted to an iPhone. The data can also be shared with friends and family, a feature Mr. Clauson noted was appreciated by his own elderly family members. AdhereTech, similar to GlowCap, is a smart pill bottle, which provides an escalating series of light and sound alerts to remind patients to take their medication. Proteus Digital Health has designed an ingestible biosensor, capable of being fixed to a capsule, transmitting direct adherence data. (Editor’s Note: In May, Proteus and Otsuka resubmitted a digital medicine version of the antidepressant Abilify. FDA decision is expected in 4Q17.) Care4Today is a medical adherence platform and app that makes a small donation to a charity of the user’s choice each time a medication is taken as prescribed. Mr. Clauson finds that adding these touchpoints as motivation is imperative in driving medication adherence, and recommended educators to keep an eye out for these kinds of features.
• The audience was surprised to hear that Android smartphones are more common in the US than iPhones (53% of smartphone users vs 44%). Yet, most healthcare apps and digital health tools are targeted to iPhone users. Mr. Clauson advised educators to consider their patient population before recommending technology, keeping access in mind. The audience was further shocked to learn that ~70 million people in the US use pay-as-you-go phones, barring utilization of new digital solutions for those who arguably need it most. And even for those who do use smartphones, some use it in very different ways than we might expect, an issue that UCSF’s Dr. Courtney Lyle’s explored at the Digital Diabetes Congress in January.

Diabetes Therapy

Cardiovascular Risk Management in Diabetes Mellitus

Anthony McCall, MD, PhD (University of Virginia, Charlottesville, VA)

In a comprehensive review of new tools for CV risk management in diabetes, Dr. Anthony McCall noted that cardiologists seem enthusiastic to prescribe SGLT-2 inhibitor empagliflozin (Lilly/BI’s Jardiance) and GLP-1 agonist liraglutide (Novo Nordisk’s Victoza) to prevent CV outcomes and especially death. These two diabetes drugs demonstrated CV benefit in EMPA-REG OUTCOME and LEADER, respectively, and Jardiance has even received an expanded indication for the reduction of CV death (a CV indication for Victoza is still under FDA review, though it has been granted by the EMA for the European label). Dr. McCall told the story of the nail-biter 12-11 Advisory Committee vote in favor of the Jardiance label update: This panel was half cardiologists, half endocrinologists, and all the heart doctors favored approval. Since then, the ACC has hosted several colloquia on these glucose-lowering, cardioprotective therapies, and according to Dr. McCall, cardiologists have been passionate about prescribing these products for the CV benefits alone. Lilly/BI recently announced their support for an ACC program aimed at improving diabetes care within cardiology settings (likely to increase uptake of Jardiance within cardiology clinics), and indeed, one of the major real-world implications of positive diabetes CVOTs is that cardiologists have been officially invited into diabetes management. We’re glad to hear about general excitement for empagliflozin and liraglutide from that field. We hope diabetes care providers also show growing enthusiasm moving forward – the ADA’s endorsement of empagliflozin and liraglutide for CV risk reduction in its 2017 Standards of Care is a very good start. That said, Dr. McCall suggested that endos on the Jardiance Advisory Committee may have been more skeptical about the statistical significance of the EMPA-REG OUTCOME results because the hazard ratios for “on treatment” analysis and “protocol” analysis crossed the line of unity, whereas the upper bound of the 95% confidence interval for “intent to treat” analysis was <1.00. A theme emerging from ESC 2016 was that endocrinologists on the whole may be waiting for more clarity on Jardiance’s mechanism of CV benefit, but several diabetes thought leaders at EASD 2016 argued fervently that mechanism doesn’t matter when you have a medicine that prevents death. Said Dr. Juris Meier, “at a certain point, it’s okay to be pragmatic and say even if we don’t know exactly how we’re saving lives, let’s save lives.” We couldn’t agree more. There is a lot of room here for better patient education – the mindset of patients and doctors currently is not in complication prevention and this must change to reach ultimate success.

• Dr. McCall acknowledged that most real-world patients won’t perfectly match the average participant profile in a diabetes CVOT, but he still advocated for the use of Jardiance and Victoza. It’s true that the CV effects in these trials were driven by a high-risk cohort – this was a major point of debate at the recent FDA Advisory Committee meeting to discuss the potential Victoza label change. Dr. McCall presented a case study of a patient facing lower CV risk, without established CV disease, but explained that there’s still reason to favor the SGLT-2 or the GLP-1 over other therapeutic options. He pointed out that diabetes confers the same approximate relative risk increase for MI as having had a previous MI (but no diabetes), which means that diabetes itself puts people in a higher-risk group. Investigating these agents in primary prevention is a future direction for research. To this end, we look forward to results from the DECLARE trial of AZ’s SGLT-2 inhibitor Farxiga (dapagliflozin), as this diabetes CVOT has enrolled the largest primary prevention population to-date (~50% of 17,276 total participants). The CANVAS trial of J&J’s SGLT-2 inhibitor Invokana (canagliflozin) enrolled ~33% of 10,142 total participants with CV risk factors but no established CV disease. Full results were presented at ADA 2017, and showed no significant interaction between risk reduction for three-point MACE and the higher-risk vs. lower-risk subgroups, which is early indication that canagliflozin may be cardioprotective in people with type 2 diabetes but no history of CV events, though the evidence for primary prevention isn’t conclusive at this point.
• Dr. McCall recommended prescribing empagliflozin instead of canagliflozin to type 2 patients with peripheral vascular disease. The CANVAS study found a nearly two-fold risk for lower limb amputations associated with canagliflozin vs. placebo, but as many thought leaders have pointed out, real-world amputation risk is quite low without other underlying factors like peripheral vascular disease. Proper patient selection for Invokana could mitigate this risk, and we also emphasize the need for stronger education around foot care/monitoring for ulcers. Interestingly, Dr. Kittie Wyne also brought up the confounding issue of peripheral vascular disease in her Saturday talk at AADE, calling for a dedicated study that investigates appropriate medications for diabetes patients with this comorbidity. We’d be intrigued to see this trial come to fruition, and we appreciate any insight right now on using canagliflozin vs. empagliflozin in clinical practice. Overall, we feel it’s impossible to adequately compare CANVAS and EMPA-REG OUTCOME due to differences in trial design – how amputations were adjudicated (prospectively in CANVAS vs. retrospectively in EMPA-REG OUTCOME), length of data collection, etc. – but it’s reassuring to hear providers like Dr. McCall allude to a continued role for Invokana in diabetes care with risk mitigation in mind. We also can’t pass up any opportunity to urge more standardization in CVOT design, perhaps starting with FDA guidance on this.

Insulin Monotherapy for Patients with Type 2 Diabetes and Uncontrolled Blood Glucose on High Doses of Insulin

Jonathan Marquess, PharmD (Institute for Wellness and Education, Woodstock, GA)

Dr. Jonathan Marquess delivered a practical, engaging presentation on the benefits of Lilly’s Humulin U500 (human insulin), although some limitations to human insulin inevitably came up during Q&A, reminding us of the major trade-offs. He encouraged audience members to re-imagine the “appropriate” patient for U500 insulin as anyone requiring >200 units per day – higher concentration insulin means lower volume injections and better insulin absorption. Humulin showed an impressive 1.2% A1c reduction in the U-500 Initiation Trial (n=323) after 24 weeks of twice-daily dosing, and showed a 1.1% A1c reduction with thrice-daily dosing. Moreover, Dr. Marquess described how Humulin has both basal and prandial properties, with onset of action within 30 minutes and duration of action out to 24 hours. On the other hand, Humulin was associated with a mean ~5 lbs weight gain in both twice-daily and thrice-daily dosing groups in the Initiation Trial. The Humulin U500 KwikPen is designed for high doses, delivering up to 300 units in a single injection, but it does dial in five-unit increments and thus requires rounding of doses down to multiples of five. Dr. Marquess did note in his slides that the Humulin KwikPen is the lowest-priced insulin pen on the market on a per-unit basis, but payer coverage is a separate story. Dr. Marquess explained that insurance companies will “say it’s not covered if you call, but there is a prescription card to get Humulin for as little as $25/month.” Humulin is preferred over Novo Nordisk’s human insulin product Novolin on the Express Scripts formulary, but is excluded from the CVS Health formulary. Dosing errors can be common with Humulin U500, so Dr. Marquess cautioned that the ultra-concentrated insulin should be administered only via KwikPen or via BD’s dedicated syringes for U500 insulin, which need to be prescribed. Audience members offered stories of patients experiencing severe hypoglycemia after being given the wrong syringes at the pharmacy (when prescribed vial insulin), or not being given pen needles (when prescribed the KwikPen). Dr. Marquess reiterated that patient education is particularly important when prescribing U500 insulin. All in all, this product theater confirmed our view on human insulin – the low cost cannot be overlooked, given the many people with diabetes who face access/affordability challenges, but it’s also unfortunate that the trade-off for low-cost is a more complicated dosing regimen (for an already difficult-to-titrate therapy), heightened hypoglycemia risk, and weight gain (this is particularly aversive to patients, and has been cited by several thought leaders as a reason for low insulin adherence). We also note that a single hypoglycemia hospitalization might cancel out the supposed cost-savings of Humulin or another human insulin product, and we urge payers to think about this in making coverage decisions (Novo Nordisk’s next-gen basal insulin Tresiba, for instance, showed a significant hypoglycemia benefit vs. Sanofi’s Lantus in the DEVOTE trial). For more insights on human insulin, see our coverage of a recent JAMA viewpoint defending human insulin for type 2 patients, authored by Drs. Kasia Lipska, Irl Hirsch, and Matthew Riddle.

Intensifying Insulin Therapy with GLP-1 Receptor Agonists

Evan Sisson, PharmD (VCU School of Pharmacy, Richmond, VA), John Bucheit, PharmD (VCU School of Pharmacy, Richmond, VA)

Drs. John Bucheit and Evan Sisson discussed similarities and differences between agents in the GLP-1 agonist class, arguing that they all offer remarkable A1c-lowering efficacy, but some distinguish themselves through ancillary effects on weight loss, CV risk, and medication adherence. Dr. Sisson explained how exenatide (AZ’s once-weekly Bydureon) and dulaglutide (Lilly’s once-weekly Trulicity) have shown more clinically-meaningful weight loss compared to albiglutide (GSK’s once-weekly Tanzeum), which corroborates our sense that albiglutide has a weaker clinical profile vs. in-class competitors (GSK recently announced plans to withdraw support from Tanzeum and to cease manufacturing, and management suggested that the company should have known from the start, based on clinical data, that the product would face substantial challenges on the commercial landscape). Liraglutide (Novo Nordisk’s once-daily Victoza) offers the distinct advantage of cardioprotection, as seen in the LEADER trial. Dr. Bucheit particularly emphasized the 22% risk reduction for CV death (HR=0.78, p=0.007), what he called “the most important outcome,” given that this is by far the leading cause of death for people with diabetes. No other GLP-1 agonist on the market has demonstrated a CV benefit, and Victoza may gain further advantage if the FDA approves a new CV indication for the drug – we have high hopes following the 17-2 Advisory Committee vote in favor, and following the EMA’s approval of a similar indication, but we’re not uncrossing our fingers until we see this important label expansion come through. Notably, the REWIND CVOT for Trulicity is ongoing with an expected completion date of July 2018. The ELIXA and EXSCEL CVOTs for Sanofi’s Adlyxin (lixisenatide) and AZ’s Bydureon, respectively, are complete and have found CV safety but not efficacy. On medication adherence, Dr. Bucheit suggested that a once-daily dosing regimen may be easier to remember, which would give Victoza an edge over Bydureon and Trulicity despite its 7x injection burden. He underscored that adherence is linked to therapeutic efficacy (i.e. patients won’t reap the glucose-lowering, weight loss, or cardioprotective benefits of any drug, no matter how potent, if they don’t take it), but also qualified that the choice between a once-daily vs. once-weekly GLP-1 agonist should be based on patient preferences. We’ve noticed high praise of GLP-1 agonists as a recurring theme at this meeting (see our coverage of Dr. Susan Cornell’s outstanding Pharmacology Boot Camp), and we appreciated this session’s focus on how GLP-1 agonists affect outcomes beyond A1c. As far as in-class competition, we feel it’s important to note that very few type 2 diabetes patients in the US are taking a GLP-1 agonist currently (only 5% of type 2s were on a GLP-1 agonist in 2013, according to a Diabetes Care article). Much of this can be attributed to access/affordability issues, but in general, we see plenty of room for multiple products in this highly-effective therapy class to be successful on the market. To that end, we’re excited by some of the upcoming innovations in GLP-1 agonist therapy outlined on one of Dr. Sisson’s slides: (i) Intarcia’s ITCA 650, an implantable mini-pump offering continuous subcutaneous release of exenatide for three-six months (FDA decision expected by December 2017), (ii) Novo Nordisk’s once-weekly semaglutide, which has already shown CV benefit in a smaller, shorter CVOT SUSTAIN 6 (FDA decision expected by December 2017), and (iii) Sanofi’s phase 2 efpeglenatide with potential for once-monthly dosing.

• Dr. Sisson touched upon the warning for medullary thyroid carcinomas (MTC) on many GLP-1 agonist product labels, a safety signal that appeared in rats but that hasn’t been significant in monkeys or humans. He posed a tongue-in-cheek question to the audience – “are your patients more like rats, or more like monkeys?” – the suggestion being that concerns surrounding MTC, which haven’t yet shown relevance in humans, shouldn’t necessarily limit use of GLP-1 agonists in clinical practice, especially considering the multitude of benefits to this drug class. This discussion came up at the FDA Advisory Committee meeting to discuss the potential Victoza label update, with panelists advocating for the removal of this black box warning on their own accord (“we all feel the CV risk reduction outweighs the MTC”). We’d hate to see a highly-effective therapy under-utilized for a safety signal that to-date, has no empirical grounds in humans, though we don’t want to diminish the critical importance of safety and quality assurance on FDA’s part. We’ll be curious to see what the FDA makes of comments collected at the Advisory Committee meeting regarding MTC.

Pharmacology Boot Camp

Susan Cornell, PharmD (Midwestern University, Chicago, IL)

In her third year offering a pharmacology boot camp as part of AADE pre-conference programming, Dr. Susan Cornell (Midwestern University, Chicago, IL) characterized GLP-1 agonists as the future of diabetes treatment – she hopes to see them as first-line therapy one day. Dr. Cornell discussed how GLP-1 agonists address six dysfunctional organs in the “ominous octet” model of diabetes – an upgrade from the four she named last year. These advanced agents (i) act on the liver to lower endogenous glucose production, (ii) enhance insulin and amylin secretion from the pancreatic beta cells, (iii) which sends more amylin to the brain and results in satiety, and (iv) slow gastric emptying from the GI tract. This year, Dr. Cornell additionally described how GLP-1 agonists (v) impair glucagon secretion from the pancreatic alpha cells and (vi) improve glucose uptake in muscle via weight loss. Moreover, the availability of both short- and long-acting GLP-1 agonists allows for individualized targeting of postprandial glucose vs. fasting glucose, respectively. Interestingly, Dr. Cornell suggested that combining a GLP-1 agonist with an SGLT-2 inhibitor would target the remaining two organ dysfunctions in the ominous octet by correcting for increased lipolysis and increased renal glucose reabsorption. On the other hand, the esteemed Dr. John Buse (UNC, Chapel Hill, NC) shared some skepticism about this particular combination of agents at Keystone 2017 and at ADA 2017. More specifically, he explained that GLP-1 agonists and SGLT-2 inhibitors may neutralize each other’s benefit, that their combined benefit would be at best sub-additive (as in AZ’s DURATION-8 trial investigating co-administration of GLP-1 Bydureon with SGLT-2 Farxiga), and that they may introduce adverse consequences due to differential effects on glucagon response. Additionally, the overwhelming chatter from educators in the room was that even with insurance, the GLP-1 class remains inaccessible for most patients. This audience response underscores the need for better reimbursement of these highly-effective agents. We find it immensely sad that these glucose-lowering, weight loss-promoting, potentially cardioprotective therapies are out there on the market, but out of reach for so many people who stand to benefit, and it seems nearly impossible to truly personalize diabetes treatment if cost is such a looming variable that settles most of the provider’s decisions. According to a recent Diabetes Care article, only 5% of US patients with type 2 diabetes were on a GLP-1 agonist in 2013. Dr. Cornell did present a case study in which she helped an uninsured patient enter a patient assistance program for Novo Nordisk’s Victoza (liraglutide) – subsequently, GLP-1 agonist therapy lowered his A1c by ~1.5%. See our coverage of Dr. Cornell’s pharmacology boot camp from AADE 2016 and 2015 – this is certainly becoming an annual favorite!

• Dr. Cornell reiterated her expressly negative view of sulfonylureas, recommending they be kicked out of diabetes treatment algorithms. “It’s time for sulfonylureas to be in the trash can. The only reason I still use them is because they’re cheap, and I can send my patients to Walmart to get them for $4.” These agents come with high hypoglycemia risk and weight gain. They’ve also been associated with beta cell burnout and possible CV risk. Given this weak safety/tolerability profile (especially compared to more advanced therapy classes), we couldn’t agree more with Dr. Cornell on sulfonylureas. Ultimately, Dr. Cornell’s talk highlighted a heavy constraint on HCPs in trying to practice evidence-based medicine: Patients can only take drugs they can afford, and many effective medicines are unaffordable. There’s much more work to be done in expanding patient access to safer, more effective drug classes, which importantly, could be cost-saving in the long run by reducing the incidence of diabetes complications (we all know how expensive a hypoglycemia hospitalization can be…).
• Dr. Cornell also highlighted new fixed-ratio combination therapies Soliqua (Sanofi’s insulin glargine/lixisenatide) and Xultophy (Novo Nordisk’s insulin degludec/liraglutide). We were glad to hear her positive endorsement of these products, since many HCPs (particularly in the US), seem reluctant to put patients on combination therapy. The outmoded treat-to-fail paradigm of diabetes management asks patients to start on individual monotherapies, which are slowly up-titrated before a combination approach is even considered – this leaves patients for far too long with poorly controlled hyperglycemia, and holds them back from a product that is known to be more effective, safer, and more tolerable vs. component monotherapies. Basal insulin/GLP-1 agonist combos were perhaps the most highly-anticipated new therapy class in the recent history of diabetes care, and we’ve been disappointed by the slow commercial uptake of both Soliqua and Xultophy to-date (although we understand these products are very new-to-market, with Soliqua launched in the US in early January and Xultophy in May 2017). That this class of combo therapy is being highlighted to diabetes educators is a reassuring sign for the future, though as Sanofi management stated on the company’s recent 2Q17 earnings call, we should expect uptake to be gradual.
• Dr. Cornell discussed four drugs as effective interventions for prediabetes: alpha glucosidase inhibitors (AGIs) and metformin are her first two choices, followed by TZDs and GLP-1 agonists. As prediabetes becomes an increasingly recognized epidemic in the US, it’s important for HCPs to be able to effectively diagnose and treat the condition with evidence-based medicines. We’d love to see a trend toward more swift interventions for type 2 diabetes prevention, but we recognize there’s a long road ahead in getting prediabetes officially recognized as a disease so that therapies can be officially indicated for it.

Using the AACE Algorithm to Get to Goal with Combination Therapy

Kittie Wyne, MD, PhD (Ohio State University, Columbus, OH)

Ohio State’s Dr. Kittie Wyne returned to AADE to advocate for combination therapy, using the 2017 AACE treatment guidelines as a framework for her (highly compelling) argument. The ADA/EASD position statements perhaps have wider influence (“more often than not, these are the guidelines people hear about”), but Dr. Wyne described the merits of the AACE algorithm – namely, that it recommends earlier intervention with combination therapy if patients are diagnosed with A1c ≥7.5%, and recommends earlier initiation of basal insulin if patients are diagnosed with A1c >9%. That said, Dr. Wyne outlined hurdles to implementing combination treatment regimens in the real world, both on the provider-side and the patient-side. While a simultaneous approach to pharmacotherapy can be effective, clinical inertia often leads HCPs to wait 18-20 months before switching or adding agents, rather than the recommended three months – how depressing! Patients tend to equate the number of pills/injections they take to the severity of their diabetes, interpreting more medications as a sign of failure (type 2 patients are particularly averse to starting insulin injections for this reason, and Dr. Wyne explained how she sets expectations from day one that insulin will likely be needed, positioning it as a question of “when?” not “if?”). Fixed-dose and fixed-ratio combination products circumvent both of these obstacles, according to Dr. Wyne – providers can get their patients on a single tablet or injection that offers superior efficacy and a milder side-effect profile vs. component monotherapies. Moreover, Dr. Wyne emphasized how combo therapy allows you to target many aspects of the “ominous octet” (if not all eight) at once, echoing Dr. Susan Cornell’s perspective from Pharmacology Boot Camp the previous day. Notably, during this pre-conference session, Dr. Cornell defended GLP-1/SGLT-2 co-administration because this duo of drugs corrects all eight dysfunctions in the ominous octet. Our sense is that commercial enthusiasm for combination therapy lags significantly behind clinical enthusiasm, which is distressing from our view given the high number of patients not at their glycemic targets. Basal insulin/GLP-1 agonist fixed-ratio combos were perhaps the most highly-anticipated new therapy class in recent diabetes history – Dr. John Buse has gone so far as to say that Novo Nordisk’s Xultophy (insulin degludec/liraglutide) may be “the most effective anti-hyperglycemic agent on the planet” – and yet real-world providers in the US seem reluctant to prescribe them, now that Xultophy and Sanofi’s Soliqua (insulin glargine/lixisenatide) are finally available. To this end, we appreciated Dr. Wyne’s endorsement of earlier intervention with combo therapy, and we very much hope to see this take root in real clinical settings. We’re eager to see better reimbursement prospects for these products as they become more established on the market, particularly as “value-based therapy” takes hold.

• In addressing the amputation signal seen for J&J’s SGLT-2 inhibitor Invokana (canagliflozin) in CANVAS, Dr. Wyne called for a dedicated clinical study of patients with diabetes and peripheral vascular disease. When asked to share her two cents, she admitted “I really don’t know the answer,” but briefly discussed how many people with amputations in the CANVAS trial had baseline peripheral vascular disease, which heightened their risk for this adverse event. She mentioned that much more research is needed to better understand which therapeutic agents are safe and effective for this particular element of the diabetes patient population. Referring to the broader implications of CANVAS results, Dr. Wyne shared, “I can’t tell you we should take patients off this drug and put them on another,” because this outcomes trial has left us more questions than answers, at least for now, until post-hoc analyses further elucidate the safety signal. She added, “if someone’s doing well, and is stable on any therapy, I wouldn’t recommend changing it.”

The New Concentrated Insulins: Is U-500 Becoming a Dinosaur?

Wendy Lane, MD (Mountain Diabetes and Endocrine Center, Asheville, NC)

In an engaging morning session, Dr. Wendy Lane shared actionable advice on type 2 diabetes management in patients with high insulin requirements.  She set the stage with a statement on the scope of high-dose insulin therapy, noting that ~35% of people with type 2 diabetes need an insulin maintenance dose of 60 units/day or more. In one treat-to-target basal insulin trial, 21% of patients required >80 units/day. Dr. Lane pointed to the rising tide of obesity, a major cause of insulin resistance, as the primary driver of increasing insulin requirements. She lamented that this has not been met with a corresponding influx of therapies tailored for patients with high insulin requirements, but spoke to the few viable options that are out there. Concentrated next-generation insulins – namely Sanofi’s Toujeo (insulin glargine U300) and the U200 version of Novo Nordisk’s Tresiba (insulin degludec) – allow for smaller injection volumes, which are (i) more comfortable and are (ii) more consistently absorbed by the body (notably, Dr. Jonathan Marquess mentioned these same two features of ultra-concentrated insulin to advocate for Lilly’s Humulin in a day #3 product theater). Dr. Lane pointed out room for improvement on the adherence-friendliness front, given that the 80-unit maximum dose of typical insulin pens forces patients with high insulin requirements to take more than one injection per dose. Larger maximum doses and a higher volume pen would allow for fewer injections and fewer prescription refills alike – a win on all fronts. The most concentrated insulin available, U500 regular insulin (including Lilly’s Humulin), is both a blessing and a curse in Dr. Lane’s eyes because it has both basal and prandial activity (again, this echoed Dr. Marquess’ comments from the previous day). This is advantageous for addressing postprandial spikes, but makes dose timing difficult and places patients at risk of stacking. For this reason, Dr. Lane deemed U500 insulin a “dinosaur” for anyone with insulin requirements <300 units/day. For those who require a very high dose, the reduced injection burden that comes from super-concentrated U500 insulin may outweigh other concerns, though this decision should be made on a case-by-case basis, according to Dr. Lane.

• Dr. Lane remarked that the inability to use concentrated insulins in CSII is a major shortcoming in diabetes care. Though the majority of concentrated basal insulins (U300 insulin glargine, U200 insulin degludec, and U500 regular insulin) come in vials that allow pump use, the majority of pumps are only configured for U100 insulin. Dr. Lane described her own experience using concentrated insulin in CSII off-label – a process which requires potentially error-prone mathematical conversions for pump settings – calling on diabetes technology companies to make a dedicated pump for the growing number of patients with high insulin requirements. Dr. Lane expressed particular frustration over the one existing concentrated rapid-acting insulin, U200 insulin lispro, which comes only in pen form, thus necessitating a complex regimen of drawing the insulin out of the pen with a syringe in order to use the product in a pump. She conveyed this sentiment in the form of a poem: “U500 in pumps made us smile. But when bloused it lasts quite a while. Not the case you know for U200 lispro – can we please put it into a vial?!”
• We were pleased to hear Dr. Lane advocate for the use of insulin-sparing adjunct therapies such as GLP-1 agonists and SGLT-2 inhibitors to address postprandial spikes and control weight gain. The use of such agents may lower insulin requirements, resulting in more comfortable injections at smaller volume and possibly fewer injections overall. Limiting weight gain is another major advantage of reduced daily insulin dose, and this would be in addition to existing weight-lowering effects of GLP-1 agonists and SGLT-2 inhibitors. Perhaps the greatest benefit of these adjunct therapies, according to Dr. Lane, is their ability to lower glycemic variability – a crucially important outcome beyond A1c with strong ramifications for everyday well-being and quality of life. “Keep your ears open, it will be all about glycemic variability soon!” she noted – music to our ears! We certainly appreciate the increasing emphasis on glycemic variability (and time-in-range, for those on CGM) among providers and hope to soon see a corresponding focus on this in the regulatory sphere. The diaTribe Foundation’s recent Consensus Conference on Glycemic Outcomes Beyond A1c was an valuable step in the right direction, we believe – see our full report for more on this movement.

Seniors with Diabetes: Why Are They Different?

Terry Compton (St. Tammany Parish Hospital, Covington, LA), Sara Reece (Philadelphia College of Osteopathic Medicine, Suwanee, GA)

Two all-star educators, Ms. Terry Compton and Dr. Mandy Reece, provided a practical overview of diabetes pharmacotherapy in the senior population, recommending the attenuation of glycemic goals and therapeutic intensity as patients age. Ms. Compton posited that the ADA’s general A1c goal of <7% is appropriate for older patients who are healthy, but that this target should be loosened to <8% in elderly people with serious complications and comorbidities, and even to <8.5% if patients are particularly frail with lower functional ability. Echoing sentiments we’ve heard from thought leaders such as Dr. Kasia Lipska, Ms. Compton explained that this relaxing of A1c targets is intended to balance the risk for diabetes complications (hyperglycemia symptoms, ketoacidosis) with the risk for treatment-related complications (namely hypoglycemia). Less stringent A1c goal-setting also factors in that institutionalized people with diabetes in poor health with shorter life expectancy may have less to gain from tight glycemic control in terms of avoiding micro and macrovascular complications of hyperglycemia (which appear over time). On the flip side, Dr. Jay Skyler cautioned against this reasoning at Keystone 2017, arguing that it’s a “slippery slope” to call for relaxed A1c targets based on shorter life expectancy, and we tend to agree. Instead of this broad-sweeping recommendation, we’d love for HCPs to consider CGM, patient education, and agents from more advanced drug classes to minimize hypoglycemia risk in older patients without asking anyone to compromise their desired glycemic control. To this end, Dr. Reece wasted no time pointing out the drug class to avoid in older patients – sulfonylureas. We share her concerns about the elevated risk of hypoglycemia with sulfonylureas – for all people with diabetes, but the elderly in particular – and we continue to hope for a near-term future where this class falls out of use in favor of safer agents. On a practical note, Dr. Reece discussed the unfortunate reality that sulfonylureas, due to their generic status, are one of the few diabetes medications that some patients are able to afford. In these circumstances, she recommends glipizide as one of the safer agents in the class, but cautioned the audience to prescribe this “only if you must.” Insulin, according to Dr. Reece, is another therapy to use with extreme caution in elderly patients due to its hypoglycemia risk as well as dosing complexity. She especially warned against insulin use in people with impairments in vision or motor skills, as well as those for whom an insulin regimen would be cognitively overwhelming. In line with the ADA Standards of Care, she highlighted newer agents such as SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors (in addition to metformin) as the best diabetes therapy options in elderly patients to minimize hypoglycemia risk while maintaining glucose-lowering efficacy. Indeed, we see these as reasons for the increased use of newer agents in all people with diabetes. Last but not least, we appreciated Ms. Compton and Dr. Reece’s emphasis on psychological considerations in diabetes care for the elderly (again, something that applies to all diabetes management, but especially so when treating older patients). The duo underscored the importance of vigilant monitoring for signs of cognitive impairment (which could significantly impact diabetes self-management), and advocated for depression screening to be a “high priority” in this demographic.

Review of FDA Guidance on Cardiovascular Outcomes for Diabetes Medication Trials and Application to Clinical Management

Katherine O’Neal (University of Oklahoma, Oklahoma City, OK)

Dr. Katherine O’Neal summarized the most important findings gleaned from diabetes CVOTs so far, highlighting a potential cardioprotective class effect for SGLT-2 inhibitors and more mixed data on CV benefit from GLP-1 agonist CVOTs. She set the stage by establishing diabetes as a CV disease risk equivalent. Regardless of age group, risk for CV events is magnified 2.5-4x in people with diabetes vs. the background population, and rates of CV death are 1.7x higher in people with diabetes vs. those without, according to Dr. O’Neal’s slides. We add that the recent CDC Diabetes State Burden Toolkit attributed 31% of diabetes-related deaths in 2015 to CV morbidity; without a doubt, CV disease is the leading cause of mortality among people with diabetes. All this makes CV risk reduction a critical component of diabetes management, which means providers have to be acutely aware of the differential CV effects of various drug classes, and of various agents within the same class.

• On SGLT-2 inhibitors, Dr. O’Neal reviewed the 14% relative risk reduction for the primary endpoint of three-point MACE (non-fatal MI, non-fatal stroke, CV death) seen for both Lilly/BI’s Jardiance (empagliflozin) in EMPA-REG OUTCOME and for J&J’s Invokana (canagliflozin) in CANVAS. The EMPA-REG OUTCOME study set off excitement for cardioprotective diabetes drugs – until then, these trials had demonstrated CV safety, at best – and CANVAS helped corroborate this as a very real benefit in improving CV outcomes. An FDA Advisory Committee recommended a new CV indication for Jardiance by a tight 12-11 margin in June 2016, and the agency followed suit with an expanded indication for the reduction of CV death in December. The DECLARE CVOT for dapagliflozin (AZ’s Farxiga) is expected to complete in the second half of 2018 according to AZ management. The VERTIS CV trial for Merck/Pfizer’s ertugliflozin (still pending FDA approval, with a decision expected by end of year) is expected to complete in October 2019. Both of these trials will give prescribers a better idea of any potential cardioprotective class effect for SGLT-2 inhibitors. Dr. O’Neal noted that researchers don’t yet understand the exact mechanism of CV benefit from empagliflozin or canagliflozin, suggesting that upcoming trials should help clarify this as well. Across her whole presentation, Dr. O’Neal seemed to be most impressed by the CV data for SGLT-2 agents. In our view, it’s enormously exciting that Jardiance is now the first diabetes drug with a CV indication – patients are accustomed to taking medicine to lower glucose, but now there’s a therapy available that can actually help prevent CV death. We heard from J&J management that the company plans to file with the FDA by end of September, requesting a new CV indication for Invokana.
• GLP-1 agonists have shown more inconsistent data in CVOTs, suggesting that cardioprotection may not be a class effect here. While Victoza (Novo Nordisk’s liraglutide) demonstrated an impressive 13% risk reduction for three-point MACE in the LEADER trial, Adlyxin (Sanofi’s lixisenatide) showed neutral CV effects in ELIXA, and topline results from the EXSCEL trial revealed neutral CV effects for Bydureon (AZ’s exenatide once-weekly) as well. An FDA Advisory Committee recently voted 17-2 in favor of granting a CV indication to Victoza based on LEADER data (the EMA recently approved this CV indication for Victoza’s European label). Ultimately, cardioprotection may not be a class effect for GLP-1 agonists although it may also be that some percentage of trials could be too short to show the impact. We look forward to the presentation of full EXSCEL results at EASD 2017 for more insight into these differential CV effects. One theory (pure speculation, at this point) is that human GLP-1-based drugs are showing a CV benefit (this applies to both liraglutide and Novo Nordisk’s not-yet-approved semaglutide), while exendin-4-based drugs are not (i.e. lixisenatide, exenatide once-weekly, and exenatide in a mini-pump as Intarcia’s not-yet-approved ITCA 650).
• On DPP-4 inhibitors, Dr. O’Neal described the signal for heart failure hospitalization associated with AZ’s Onglyza (saxagliptin) in SAVOR-TIMI. The EXAMINE trial for Takeda’s Nesina (alogliptin) found an imbalance in heart failure hospitalizations, with more occurring in the alogliptin group vs. placebo, but this did not meet criteria for statistical significance. Still, the FDA added warnings for heart failure to the Onglyza and Nesina labels in April 2016. Notably, the TECOS trial of Merck’s DPP-4 inhibitor Januvia (sitagliptin) reported a decidedly neutral hazard ratio of 1.00 for heart failure hospitalization, but the FDA issued a Complete Response Letter for inclusion of this data on the product label. Overall, Dr. O’Neal didn’t voice her personal clinical opinion one way or the other on DPP-4 inhibitors and any possible heart failure risk.
• After reviewing the evidence, Dr. O’Neal concluded that the current sequence of drugs in diabetes treatment algorithms should not be changed. She defended metformin as first-line therapy, pointing to positive CV effects associated with the drug in UKPDS. While we recognize metformin’s advantage of low cost and reasonable safety/efficacy, we also want to note the danger of putting too much faith in metformin: Too many patients remain on first-line therapy with no changes or additions to their treatment regimen for far too long, due to clinical inertia and other real-world factors. Now that we have cardioprotective therapies in our treatment arsenal, we’d love to see those used earlier on in the course of disease. In fact, Dr. Jay Skyler recently argued at Keystone 2017 that metformin is overemphasized in guidelines and that DPP-4 inhibitors should be phased out of diabetes management, replaced with GLP-1 agonists and SGLT-2 inhibitors, agents that might offer cardioprotection rather than neutral CV effects and possible heart failure risk. We do see DPP-4 inhibitors as having the cleanest side-effect profile of any drugs and believe they have a place with some newly diagnosed patients in particular.

A Novel Strategy for the Management of Inpatient Hyperglycemia in Patients with Type 2 Diabetes

Guillermo Umpierrez, MD (Emory University, Atlanta, GA)

In a very well-attended talk, Emory University’s Dr. Guillermo Umpierrez re-evaluated current recommendations for inpatient management of diabetes, advocating for basal-bolus therapy instead of premixed insulin, and for greater reliance on DPP-4 inhibitors. First, he offered some background on an often-overlooked topic in diabetes care (an issue he spoke to at Keystone 2017 as well). Inpatient diabetes admissions are on the rise, and hyperglycemia in the hospital is associated with significantly heightened complication risk. Hyperglycemia in the hospital affects patients without diabetes as well – stress hyperglycemia (maximum blood glucose reading of 180 mg/dl in the first 48 hours post-admission) is associated with 36% greater risk of complications, including pneumonia, acute renal or respiratory failure, acute MI, bacteremia, and death. As such, Dr. Umpierrez argued that all patients should be assessed for a history of diabetes and should be given a laboratory blood glucose test upon hospital admission. Currently, non-ICU guidelines generally recommend a glucose target of 140-180 mg/dl for most patients with type 2 diabetes – which notably, is <180 mg/dl as stipulated in ADA’s Standards of Care since 2016 – with reassessment of therapy if blood glucose drops <100 mg/dl. Insulin is currently the preferred therapy for managing inpatient diabetes, as opposed to oral agents, but Dr. Umpierrez attributed this to a lack of sufficient data on inpatient use of oral agents. Recent research into this therapy area, presented at ADA 2017, found that treatment with DPP-4 inhibitor linagliptin (Lilly/BI’s Tradjenta) following hospital discharge achieved similar glycemic control vs. basal insulin glargine (Sanofi’s Lantus) with a significantly lower frequency of hypoglycemia (3% of linagliptin patients vs. 37% of glargine patients experienced blood glucose <70 mg/dl, p<0.001). Dr. Umpierrez explained that DPP-4 inhibitors appear to be safe as inpatient therapy as well, and they come with the added benefit of fewer injections. A study comparing inpatient treatment with sitagliptin (Merck’s once-daily Januvia) vs. sitagliptin/basal insulin glargine vs. a basal-bolus regimen with insulin glargine/mealtime insulin lispro (Lilly’s Humalog) found that sitagliptin/basal insulin resulted in the best glycemic control among participants with mean blood glucose >180 mg/dl (though there was no significant difference between treatment arms for patients with mean blood glucose <180 mg/dl). Ultimately, Dr. Umpierrez encouraged HCPs to consider current blood glucose levels, duration of diabetes, and A1c in determining the course of treatment for inpatient hyperglycemia, and he suggested that further research is necessary to fully understand the potential benefits of DPP-4 inhibitors in hospital settings.

• Dr. Umpierrez’s most emphatic advice was to treat inpatient hyperglycemia with a basal-bolus dosing regimen rather than a sliding scale of 70/30 premixed insulin. The RABBIT-2 trial, which randomized 130 insulin-naïve non-ICU patients to basal-bolus therapy with insulin glargine/insulin glulisine (Sanofi’s Apidra) or to sliding scale insulin (the standard of care), found no significant difference in hypoglycemia between the two dosing algorithms, but found significantly higher average blood glucose in the sliding scale arm (~180 mg/dl vs. ~140 mg/dl, p<0.01). The RABBIT-2 Surgery trial similarly found that basal-bolus therapy achieved superior glucose control vs. sliding scale, and additionally showed that basal-bolus results in significantly fewer complications overall (8.6% vs. 24.3%, p=0.003). A similar study comparing basal-bolus therapy vs. 70/30 premixed insulin found no significant difference in daily control, but did find a significantly higher rate of hypoglycemia with 70/30 premixed insulin (24.2% vs. 64.1%, p<0.001). This data makes it hard to argue against the use of basal-bolus therapy instead of premixed insulin as standard of care in hospitals, according to Dr. Umpierrez, and we’ll be interested to see if this is implemented in medical education and in real-world hospital settings.

A Patient-Centered Approach to Help Awaken a Transformation for Adults with T2DM

Eden Miller, DO (Diabetes Nation, Bend, OR)

In a Janssen-sponsored product theater, Dr. Eden Miller addressed the ~two-fold risk for lower limb amputations seen in the CANVAS trial for SGLT-2 inhibitor Invokana (canagliflozin). Notably, amputations didn’t come up in detail during her prepared remarks, but this safety signal came up during Q&A due to keen interest from educators in the audience. While Dr. Miller acknowledged that amputations are not to be minimized, she also emphasized that this risk is very low in the real world and can be well-managed with diligent monitoring. In the full integrated dataset from CANVAS and CANVAS-R, there were 187 lower-extremity amputations, occurring a rate of 6.3/1,000 patient-years in the canagliflozin arm vs. 3.4/1,000 patient-years in the placebo arm. Dr. Miller likened this to increasing the chances of a rare event from 1% to 2%, or to “doubling your chances of getting hit by an asteroid” (to be clear, she underscored that this statement was only a joke to illustrate a point about base rate bias, and that amputation-related concerns are of course valid). Moreover, Dr. Miller explained how the vast majority of amputation events in CANVAS were linked to a precipitating factor, often a diabetic foot ulcer. She encouraged vigilant monitoring – “every time my patients come in, shoes are off” – and stronger patient education around proper foot care in diabetes.

• This echoes a view we’ve heard from many thought leaders in the field: Janssen’s VP of Medical Affairs for Cardiovascular and Metabolism Dr. Robert Cuddihy told us that amputations in the CANVAS trial were usually preceded by an infection or some other warning sign, and Global Therapeutic Head of Cardiovascular and Metabolism Dr. James List suggested that this safety finding could kick-start a movement toward better patient education on foot care. We’d love for J&J to be a leader in this initiative. UCLA’s Dr. Anne Peters shared that Invokana sometimes results in greater A1c-lowering and weight loss for her patients vs. Lilly/BI’s Jardiance (empagliflozin). She supported Dr. Miller’s opinion that HCPs don’t need to switch all their patients off of Invokana, especially since there are ways to avoid lower limb amputations with regular monitoring in real-world practice.
• We’d also add that CV morbidity/mortality seems to have a greater burden within the diabetes patient population vs. lower-extremity amputations (CV disease was the catalyst for 31% of diabetes-related deaths in 2015, according to the CDC), so this safety signal shouldn’t completely overshadow canagliflozin’s significant 14% risk reduction for three-point MACE (non-fatal MI, non-fatal stroke, and CV death). That said, a risk/benefit analysis of CANVAS showed that for every 1,000 patients treated with canagliflozin for five years, 23 fewer MACE events and 17 fewer heart failure hospitalizations could be expected, but also 15 additional lower limb amputations (10 at the level of the toe/forefoot, five above the ankle). This is a murky risk/benefit profile that will need much more unraveling through post-hoc analyses of CANVAS and CANVAS-R; to date, very respected diabetes care providers continue to voice support for Invokana and for the SGLT-2 class, despite the FDA issuing a boxed warning for amputations on all canagliflozin-containing medicines, and despite the EMA investigating this risk for all SGLT-2 inhibitor products.
• Dr. Miller was limited in what she could say about Invokana’s CV benefits since these haven’t yet been incorporated on the product label in any form, but she urged educators to read the NEJM paper on integrated CANVAS results. We learned from Dr. List that J&J plans to file a Supplemental New Drug Application (sNDA) with the FDA requesting a CV indication for Invokana by end of September, and we’d be happy to see this product join the ranks of Jardiance, which is now indicated for the reduction of CV death.

Strategies to Improve Adherence to Insulin FDC in T2D Patients: Are You Up to Speed

Davida F. Kruger (Henry Ford Medical Center Endocrinology, Detroit, MI), Maggie Powers, PhD (Powers and Associates, San Francisco, CA), Curtis Triplitt, PharmD (Texas Diabetes Institute, San Antonio, TX)

Ms. Davida Kruger, Dr. Curtis Triplitt, and Dr. Maggie Powers discussed strategies to educate patients on basal insulin/GLP-1 fixed-ratio combination therapy Soliqua (this was one of two simultaneous Sanofi corporate symposia). We were intrigued by the idea that Soliqua (insulin glargine/lixisenatide), as a very new product, might be able to circumvent the common misconception from patients that taking more medications signifies diabetes failure. The speakers listed this misconception as one of the major barriers to advancing a patient’s treatment regimen. The mental association of insulin initiation with failure is particularly sharp for many people with type 2 diabetes, which is why basal insulin therapy is often delayed well past when it would be most beneficial. Soliqua, on the other hand, could be presented as a newly-available option free of these associations. Dr. Powers suggested that it be characterized to patients as an “adjunct” treatment, something that offers superior glucose-lowering compared to basal insulin or lixisenatide alone. Dr. Triplitt described how Soliqua “pathophysiologically, makes a lot of sense,” in that it targets seven of eight organs in the “ominous octet” (all except the kidneys) – explaining this to patients makes the combo therapy seem like a logical choice rather than a punishment because their A1c is above goal, a way to correct almost all of the dysfunctions underlying their diabetes with one injection instead of two (and one co-pay instead of two). Moreover, Dr. Triplitt pointed to the milder side-effect profile of Soliqua vs. insulin glargine or lixisenatide monotherapy, which is something that definitely matters to patients. Dr. Powers emphasized that shared decision-making is key to success in diabetes care – patients have to choose Soliqua (or any therapy, for that matter) after developing a clear understanding of the advantages and limitations. In our view, basal insulin/GLP-1 agonist fixed-ratio combinations are an incredibly exciting addition to the diabetes treatment arsenal. These products (also including Novo Nordisk’s Xultophy) have been highly-anticipated in the field, and now that they’ve finally arrived on the market, we’re disappointed not to see greater uptake (Soliqua sales totaled just $4 million in 1Q17 and $6 million in 2Q17). Poor reimbursement is one obstacle, but reluctance from HCPs to prescribe a fixed-ratio combination should not be a factor restricting patients from access to the most advanced therapeutic agents. We’d love for all patients to be well-informed about this new treatment option, whether or not they decide to take it. The concept of capitalizing on Soliqua as a “new” product is interesting, and we’ll be keeping an eye on Sanofi’s marketing efforts to see if this is rolled out in other ways.

Medication De-Prescribing in Patients with Diabetes After Implementing Lifestyle Changes

Rohit Moghe, PharmD (Jefferson University Hospital, Philadelphia, PA)

Dr. Rohit Moghe shared his take on medication “deprescribing” for patients who have successfully implemented lifestyle changes, generally espousing that when it comes to diabetes drugs, it may be a case of “the fewer the better.” He noted that the FDA’s drug approval process is accelerating, and that therapies are sometimes approved with no known benefit to all-cause mortality. He argued that we don’t know how safe it is to have patients on multiple agents from different drug classes, and suggested that we are overusing healthcare resources while underusing lifestyle interventions – though prescription drugs themselves account for only ~10% (2015 data) of overall US healthcare spending (with many more dollars going toward hospital visits). In Dr. Moghe’s view, simultaneous use of >one pharmacotherapy increases risk for treatment-related adverse events, which causes unnecessary trips to the emergency room. However, we feel it is important to note that many combination regimens incorporating more advanced diabetes therapy (i.e. basal insulin + GLP-1 agonists) reduce complications like hypoglycemia, which leads to many unnecessary (and expensive) hospitalizations. Dr. Moghe implied that evidence does not support micro- or macrovascular benefits to tight glycemic control over less stringent glycemic control in older people with diabetes, and he added that the risks of hypoglycemia and other side-effects may outweigh the positive glycemic impact of aggressive pharmacotherapy in elderly patients. This debate is a hot topic in diabetes care at the moment, and we note that time-in-range has substantial quality of life benefits for people living with diabetes.  We recently heard Dr. Jay Skyler argue at Keystone 2017 that it’s a dangerous slippery slope to set higher A1c goals for older patients simply because they have lower life expectancy – we completely agree on this and think there is way too much room here for misinterpretation. While we appreciated Dr. Moghe’s practical action steps to deprescribe medication where appropriate – (i) pre-contemplation to introduce the idea, (ii) contemplation of starting points and pros/cons, (iii) preparation of a patient for a plan that works for them, (iv) action with progress monitoring and risk mitigation, and (v) maintenance with self-reflection and support – we cannot over-emphasize the importance of this issue, given that combination regimens can actually be highly effective for many people with diabetes. Moreover, we think it would be more effective to emphasize pharmacotherapy as a tool to support lifestyle modification, especially considering that newer drug classes offer lower hypoglycemia risk, weight loss (as opposed to weight neutral effects or weight gain), and other clinically-meaningful health improvements. Ultimately, the bigger question may be: How do we enhance lifestyle change to make medication de-prescribing possible without sacrificing glycemic control or other outcomes beyond A1c, and how do we make it easier for people with diabetes to engage with and adhere to diet/exercise modifications?

Zeroing in on A1c Targets: Pinpointing the Optimal Basal Insulin Strategy in Every Patient with Type 2 Diabetes

Nathan Painter, PharmD (UCSD, San Diego, CA), Teresa Pearson (Innovative Health Care Designs, Minneapolis, MN), Guillermo Umpierrez, MD (Emory University, Atlanta, GA)

A second, absolutely packed Sanofi-sponsored symposium delved into the clinical challenges of optimizing basal insulin therapy in people with type 2 diabetes. We always appreciate the incredibly practical and actionable content at AADE, and this was certainly no exception. Below we include our favorite pearls of wisdom from Dr. Nathan Painter, Ms. Teresa Pearson, and Dr. Guillermo Umpierrez.

• UCSD’s Dr. Nathan Painter criticized the epidemic of “overbasalization” in people with type 2 diabetes, pointing to the addition of a GLP-1 agonist or rapid-acting insulin as a better way to address postprandial glucose. He underscored that the efficacy of basal insulin decreases after the dose exceeds 0.5 units/kg, and larger doses only increase the patient’s risk of weight gain and hypoglycemia without providing additional benefit in A1c-lowering or postprandial glucose control. “We have to stop pushing basal up,” he argued, urging the audience to add an additional agent when basal insulin is no longer enough. Of the available basal insulin intensification options, Dr. Painter recommended a GLP-1 agonist as the next agent on board, given this class’ association with weight reduction. Though this wasn’t mentioned in the presentation, we note that switching to a basal insulin/GLP-1 agonist fixed-ratio combination would have a similar effect to adding a GLP-1 agonist on top of basal insulin therapy, while reducing injection burden and the number of prescriptions the patient needs to fill. Of course, the lack of mention is understandable considering that a simultaneous Sanofi-sponsored symposium going on across the hall from this one discussed everything educators need to know about this fixed-ratio combination class of Soliqua (insulin glargine/lixisenatide) and Novo Nordisk’s Xultophy (insulin degludec/liraglutide).
• Ms. Teresa Pearson discussed strategies to overcome patient/provider reluctance to initiate basal insulin therapy, emphasizing that diabetes educators have a particularly important role to play in breaking this all-too-common trend in primary care settings especially. Ms. Pearson began with an outline of reasons HCPs might resist initiating insulin: they think it’s complicated, it takes time to adjust and teach, they’re concerned about hypoglycemia, or they believe insulin is only to be used as a last resort. Because of these barriers, insulin therapy is delayed far too often. According to Ms. Pearson, ~50% of the time HCPs have not yet initiated insulin therapy even when a patient’s A1c exceeds 9%, resulting in many years of undue glycemic burden. In initiating basal insulin therapy, Ms. Pearson recommended using a patient-directed treat-to-target titration approach, with involves algorithms to help patients reach targets on their own, much more quickly than they would using provider-directed titration. Trials have shown this method results in better outcomes and empowers patients, without compromising safety. To further improve the patient experience, Ms. Pearson advised that educators openly discuss with patients their potential fears of weight gain, the natural progression of insulin resistance and the likely need for more agents in the future, and of course, the cost of insulin therapy. From vast personal experience with such conversations, Ms. Pearson noted that most patients who fear injections are relieved to see the small size of the subdermal needles used today, and advised doing a practice injection early on in the appointment to swiftly address this potential fear and to allow patients to focus on the other information they’re receiving without anxiety over an impending injection. To this end, we appreciated Ms. Pearson’s reminder that only 12% of Americans are truly “health literate,” so discussions of insulin dosing and safety must take place in clear, understandable, non-scientific terms.
• Emory University’s Dr. Guillermo Umpierrez led the audience through the history of innovation in basal insulin therapy, from NPH to insulin analogs to next-generation basals, emphasizing that among these many options “the real-world choice depends on the patient.” He focused particularly on the next-generation basal insulins, Novo Nordisk’s Tresiba (insulin degludec) and Sanofi’s Toujeo (insulin glargine U300), overviewing clinical data to support their flat and long-lasting action profiles. To-date, there is no data directly comparing Toujeo vs. Tresiba (though a head-to-head PK/PD trial is ongoing), so rather than emphasizing the difference between these two newer agents, Dr. Umpierrez focused on the benefits they offer over older insulin analogs – namely, a more flexible dosing window and reduced risk for hypoglycemia. We note that only Tresiba has a flexible dosing claim on its label )despite anecdotal reports that Toujeo can also be dosed in this way, and that Toujeo’s hypoglycemia findings come primarily from real-world studies such as DELIVER-2, in contrast to larger-scale phase 3 data to support a hypoglycemia benefit for Tresiba vs. standard of care Lantus in the SWITCH 1 and 2 trials and the recent DEVOTE CVOT. “For a while we were concerned with efficacy, but in the last few years the tide has turned to safety,” he remarked, positioning Toujeo and Tresiba as ideal options for basal insulin patients who struggle with hypoglycemia or find it difficult to remember to take their insulin dose at the same time each day. Conscious that next-generation insulins are unfortunately much less accessible than insulin analogs (and certainly NPH), Dr. Umpierrez closed with a nod toward practicality, emphasizing that insulin choice is multifactorial and comes down to a complex equation of cost vs. injection frequency preference vs. variability of lifestyle vs. ease of regimen vs. managing hypoglycemia risk – a difficult decision that diabetes educators are well-positioned to guide patients through.

The Role of Inhaled Insulin in the Management of Patients with Diabetes

Jerry Meece (Plaza Pharmacy and Wellness Center, Gainesville, TX)

In a MannKind-sponsored product theater, Mr. Jerry Meece emphasized the importance of postprandial glucose control in getting to target A1c, and carved out this niche for inhaled insulin Afrezza. Mr. Meece showed how postprandial control becomes the limiting factor for patients as they approach A1c goals. When A1c >10.2%, fasting glucose explains the large majority of glycemic control (70%), but this drops as A1c enters the 8.5%-9.2% range, when fasting blood sugar accounts for only 55% of glycemic control and postprandial accounts for 45%. Once A1c reaches <7.3%, postprandial glucose now explains 70% of glycemic control. This is where Afrezza could have its greatest impact – the faster onset/offset allows for tight control of postprandial excursions with less risk of hypoglycemia or insulin stacking – although Mr. Meece outlined several patient archetypes who could benefit from inhaled mealtime insulin, including the individual with type 2 who is resistant to insulin initiation but not at goal despite treatment with oral agents, the individual worried about increasing his/her injection burden, the individual who wants more discretion in bolusing to avoid being known as “the sick friend,” and anyone on CGM. Each seat at the product theater came with a demo kit and Afrezza dosing guide, and Mr. Meece praised the inhalation device for its ease-of-use and patient-friendly nature. Chatter from educators in the room revealed much intrigue and excitement about Afrezza and how to use it safely/effectively. There was quite a long list of questions asked during Q&A (despite the early 6 am hour!), which even pushed the session into overtime. Mr. Meece directed audience members to MannKind’s exhibit hall booth to get all their lingering questions answered. See our coverage of this booth below (we noticed the company’s exhibit hall presence was substantially larger than we’ve seen at recent conferences). We recommend you read this recent stirring blog post from a patient who couldn’t get coverage for Afrezza despite benefitting enormously from the product, which further reinforces positive patient feedback for MannKind’s inhaled insulin.

Big Picture

Diabetes Prevention

New Models of Care: Diabetes and the Triple Aim

Robert Gabbay, MD, PhD (Joslin Diabetes Center, Boston, MA)

Joslin’s Dr. Robert Gabbay painted a picture of what value-based care will look like in diabetes, describing a new role for diabetes educators in this shifting paradigm of healthcare reimbursement. Value-based care is grounded in the Triple Aim, which encompasses (i) improved patient experience, (ii) reduced cost, and (iii) improved population health. The emphasis in this model is on outcomes (fee-for-value), not on number of procedures performed (fee-for-service), and Dr. Gabbay underscored that this will result in improved population health at a lower cost. He shared some history on this movement to value-based care, which began in 2015 with the passage of MACRA (Medicare Access and CHIP Reauthorization Act). This bill fundamentally changed the way Medicare reimburses HCPs by establishing the Merit-Based Incentive Payment System (MIPS) and Advanced Payment Models (APM). MIPS will determine Medicare reimbursement for 90% of providers, and data being collected this year will help set payments going into effect in 2019. Every provider will receive a MIPS composite performance score based on patients’ quality of life, resource use, clinical practice improvement activities, and meaningful use of electronic health record technology, and this score will in turn determine reimbursement. The remaining 10% of providers will fall under APMs, and will be reimbursed either in bundled payments linked to the quality and cost of a specific episode of care, or in whole patient reimbursements linked to the quality and cost for a specific population – that is, an organization is given a lump sum of money and decides how to spend it (these are called Accountable Care Organizations, and are already widespread). On a very positive note, Dr. Gabbay pointed out that private payers tend to follow trends set by Medicare, which bodes well for accelerated progress toward value-based healthcare in the mid-term future. We note a couple small victories from the private sector thus far (though so much work remains to be done): CVS Health announced a new outcomes-based program for obesity drugs going into effect in 2018, and Medtronic recently entered an outcomes-based deal with Aetna (MDI users switching to an insulin pump have to achieve a set A1c benefit, or Aetna gets a rebate from the manufacturer). Dr. Gabbay’s presentation was truly the talk of the town, with audience members commenting and Tweeting that it should have been a keynote!

• Dr. Gabbay suggested a new role for diabetes educators in a value-based system. In a fee-for-service model, diabetes education is a cost center because it works to prevent complications, while departments like cardiothoracic surgery and orthopedics are considered revenue centers. In a value-based model, when you want to spend less money, cost centers like diabetes education become savings centers. As Dr. Gabbay put it, diabetes education is inexpensive, and will thus only increase in value as our healthcare system starts to change (for the better). He presented CDEs with the opportunity to continue the legacy of diabetes as the vanguard condition for health system changes. It has long been our view that strong diabetes education could be incredibly cost-saving over time, especially as it helps patients avoid severe hypoglycemia and stay motivated in lifestyle change and medication adherence – it was great to hear that educators will only become more instrumental as the environment shifts to value-based healthcare.
• Dr. Gabbay shared strategies to facilitate the shift from treating one patient at a time to managing whole populations of patients. He suggested that the first step is measuring a population’s health, and proposed the idea of a diabetes registry, or a searchable dataset of all patients with diabetes. This is already often done within some clinical practices, and it shows that most providers overestimate the effectiveness of their care. According to Dr. Gabbay, data should be shared (blinded at first, but eventually unblinded) with the end goal of reducing variation between providers, between practices, and between regions (what a way to address health disparities, as well). The added benefit of un-blinding data, as Dr. Gabbay explained, is that HCPs are naturally competitive ­and will strive to do better if it means beating their colleagues.
• Dr. Gabbay also advocated for risk stratification. Currently, 10% of the US population accounts for two-thirds of healthcare spending. Risk stratification would proactively target services to the patients who need it the most, giving “bigger bang for your buck” by preventing emergency room visits and decreasing utilization of resources downstream. Dr. Gabbay positioned diabetes educators as the go-to for high-risk patients – this would demonstrate the value of diabetes education for overall health and long-term cost-savings, and would allow CDEs to contribute most effectively in a value-based system, serving as savings centers by promoting patient engagement. We’re certainly very interested in risk stratification, as several thought leaders at WCPD 2016 mentioned it as a way to make diabetes prevention more feasible and cost-effective at the population level.

Sharing Evidence-Based Hope

William Polonsky, PhD (Behavioral Diabetes Institute, San Diego, CA)

The great Dr. Bill Polonsky reprised his workshop on evidence-based hope, arguing that our current paradigm of diabetes management relies too much on scare tactics, and not enough on the good news: There’s been a steady increase since 1984 in the number of individuals receiving Joslin’s medals for living 50 years with diabetes, and a study published in 2014 found that people with type 2 diabetes who start on metformin therapy can expect the same life expectancy as a background population over six years (though we can’t say the same for type 2 patients who start on sulfonylureas). And why are CVOTs so expensive? As Dr. Polonsky put it, one reason is because new cardioprotective therapies are keeping patients alive and heart attack-free for longer, which means investigators need a longer study duration to accumulate a sufficient number of CV events. “This is indisputably good news, and we don’t talk about it enough.” Dr. Polonsky described the downward spiral that occurs with diabetes fatalism. When patients feel doomed by their diabetes, they’re less inclined to put energy into self-management, which results in poor clinical outcomes. This was quantified in a 2012 paper: Fatalism (defined as feelings of despair, hopelessness, or powerlessness) led to significantly lower medication adherence, worse exercise habits, and lower frequency of blood sugar testing (p<0.001 for all comparisons). Conversely, patients are motivated and more likely to be engaged in their own diabetes management when told that they might be able to avoid complications entirely with target glycemic control. In other words, “well-controlled diabetes is the leading cause of NOTHING!”. Dr. Polonsky qualified that diabetes care providers don’t want to send an incorrect message that “everything’s going to be okay” without treatment (lifestyle change and more), but that patients should know living a long and healthy life is entirely possible – he argued that this approach is much more effective, from a behavioral perspective, than scare tactics.

• Last year, when AADE 2016 took place in San Diego (home of the Behavioral Diabetes Institute), Dr. Polonsky had mugs for sale with the slogan “well-controlled diabetes is the leading cause of NOTHING!” Indianapolis was a long flight away, and he could only transport one in his suitcase, which he gifted to the great Ms. Virginia Valentine. “She’s been spreading this message of hope for a lot longer than I have,” Dr. Polonsky shared, ending this Friday-morning session on a very touching note.

Toward a Precision Medicine Approach to Diabetes Prevention

Erika Berg, PhD (American Assoication of Diabetes, Arlington, VA)

ADA’s Director of Scientific and Medical Affairs Dr. Erika Berg provided a compelling overview of early precision medicine strategies to address what she positioned as “the most important question in diabetes” – how to prevent or delay morbidity/mortality from type 2. Dr. Berg remarked that some of the richest insights into precision medicine in diabetes have come from the Diabetes Prevention Program (DPP) trial, which compared two interventions, metformin and an intensive lifestyle modification program, to prevent the onset of type 2 diabetes in people with prediabetes (n=3,234). Relative to placebo, the incidence of diabetes was reduced by 58% with lifestyle intervention and by 31% with metformin therapy, demonstrating that both are viable diabetes prevention strategies (with a slight edge for lifestyle intervention). However, Dr. Berg pointed out that the relative efficacy of lifestyle intervention vs. metformin differed in important ways between various subgroups. In people over the age of 60, lifestyle is vastly preferable to metformin, which is no more effective than placebo for diabetes prevention in this population (but this was not the case for younger cohorts in the DPP study). Similarly, lifestyle is more beneficial than metformin in people with BMI between 22-35 kg/m² – interestingly, lifestyle and metformin were equally effective prevention in people with a BMI >35 kg/m². A similar pattern holds true for gestational diabetes: lifestyle and metformin are equally effective in prevention, but metformin is no better than placebo in women without history of gestational diabetes. These results provide a basis for a more personalized approach to diabetes prevention by defining demographic factors (age, BMI, and history of gestational diabetes) that could influence whether lifestyle modification therapy or metformin is more likely to be effective. Dr. Berg alluded to a future in which this kind of precision goes much deeper than phenotype, explaining that continued data mining of DPP outcomes could eventually allow us to predict an individual’s responsiveness to metformin vs. lifestyle on the basis of their genetic profile. Indeed, this could be true for predicting responsiveness to any diabetes drug or intervention – an exciting possibility given the frustration over trial-and-error that so often characterizes diabetes therapy choice. That said, our sense is that talk about precision medicine exceeds real progress, and we’re eager to see more concrete action taken to apply precision medicine approaches in diabetes – whether to treat or prevent this chronic disease. Dr. Berg closed this informative presentation with distinct optimism, remarking that despite the monumental challenge of implementing diabetes prevention measures system-wide, the massive skillset of diabetes educators could represent a substantial part of the solution.

Best Practices for the National Diabetes Prevention Program

Ann Albright, PhD (CDC, Atlanta, GA)

CDC’s Dr. Ann Albright presented the agency’s revamped ad campaign for prediabetes awareness, featuring the same risk assessment, but this time with no voice over (only text) and animal videos. This follows the first-ever national PSA targeting prediabetes from the CDC, ADA, AMA and Ad Council launched in January 2016. Some may consider the 2016 ads starring the “humorous doctor,” “bacon lover guy,” and “busy mom” to be condescending, and the lack of voice over and reliance on visual text raises issues for those with poor English literacy.  And while the background videos of puppies, hedgehogs, and goats were indisputably adorable, we feel these PSAs would be greatly-improved with a dose of the patient perspective. Still, these efforts are critical in raising awareness of prediabetes, and according to Dr. Albright, the 2016 iteration of this campaign resulted in more than one million people (!) taking the risk assessment test. This is an impressive result, and we hope this revised ad campaign will be similarly successful, given that 88% of Americans with prediabetes are unaware of their condition. Down the line, we’d love to see more patient-centric, non-stigmatized messaging around prediabetes and its implications. Throughout her presentation, Dr. Albright delivered a rallying cry for the broader public health sphere to focus attention on diabetes prevention. The CDC released its latest statistics on diabetes and prediabetes just a couple weeks ago: 84 million Americans have prediabetes, and only 12% of them are aware. It will certainly take collaboration for many different players in public health, plus multifaceted resources, to make a dent in this population and to meaningfully reduce type 2 diabetes incidence.

• Dr. Albright stressed that the prediabetes population is extremely heterogeneous and can be stratified by risk. She recommended that the full-fledged DPP should be reserved for those in the “high” (fasting plasma glucose >100 mg/dl; NDPP score 9+) and “very high” (A1c >5.7%; fasting plasma glucose >110 mg/dl) risk groups. For those in the moderate and low risk categories, counseling in their provider’s office should be sufficient. We’re very intrigued by the idea of risk stratification within prediabetes, especially since several prevention experts at WCPD 2016 (including CDC’s Dr. Edward Gregg) suggested it as a way to make implementing the DPP cost-effective at the population level.
• One of the most exciting results from the DPP trials was that the intervention was still highly-effective when delivered by trained laypeople. This is very good news considering the scope of the prediabetes epidemic, and it presents another way to make population-level diabetes prevention more cost-effective and feasible. At WCPD 2016, CDC’s Dr. Mohammed Ali called for more training of laypeople to administer the DPP, and he presented a meta-analysis of DPP translations to show that lower-cost versions of the program could still help participants achieve clinically-meaningful weight loss, as well as reductions in A1c, fasting plasma glucose, and systolic blood pressure.
• Dr. Albright emphasized that the CDC’s National DPP is still in its implementation phase, meaning providers will need to think about refinements and improvements moving forward. Not only is this program accompanied by a strong body of evidence demonstrating substantial weight loss and delays in new-onset type 2 diabetes, but research has also shown the DPP to be cost-effective and in some cases cost-saving. In fact, Medicare-eligible patients with diabetes saved a mean $2,650 by participating in the program, according to Dr. Albright. Medicare plans to begin reimbursing the Medicare Diabetes Prevention Program in 2018, which will come as a huge win for diabetes prevention (though there’s still a lot of work to be done).

Best Practices for the National Diabetes Prevention Program

Natalie Blum (AADE, Chicago, IL); Teresa Brown (Norman Regional Health System, Norman, OK); Diana Echenique (Office of Minority Health Resource Center, Washington, DC); Carl Ellison (Indiana Minority Health Coalition, Indianapolis, IN); Anne Graves (YMCA, Indianapolis, IN); Sara Nelms (Woman’s Hospital Diabetes Education Services, Baton Rouge, LA)

In a riveting panel discussion, individuals spoke to their own experiences running a National DPP for a diverse array of populations, sharing practical tips for success. Ms. Natalie Blum mentioned that the AADE is working on a paper, scheduled for publication by the end of 2017, demonstrating the cost-effectiveness of implementing the National DPP through the AADE – we’ll be very curious to see these findings, as more cost-effectiveness research could help bolster the case for more reimbursement of the DPP. She attributed success for the AADE’s National DPP in part to having systems already in place for HIPPA compliance and billing. Mr. Carl Ellison of the Indiana Minority Health Coalition emphasized the importance of making the program accessible and fun with social gatherings like picnics, line dancing, and cooking demos. Ms. Sara Nelms, who oversees a National DPP at the Woman’s Hospital in Baton Rouge, Louisiana for individuals with gestational diabetes, echoed Mr. Ellison’s sentiments, adding that hands-on activities are especially successful in driving engagement. Ms. Nelms also suggested making behavioral interventions fit within the family, and she reminded providers and lifestyle coaches that flexibility is the name of the game when it comes to helping participants succeed in the DPP. A year can be a significant commitment for some participants, and it will be critical for coaches to offer as many scheduling options as possible. Ms. Diana Echenique of the Office of Minority Health Resource Center discussed the need to remain culturally aware. In a poignant example, Ms. Echenique described a Spanish-speaking participant who couldn’t write, but ultimately lost 26 lbs through the program with the help of a high school volunteer. By creatively utilizing her resources, Ms. Echenique was able to change this woman’s life. Ann Graves of the YMCA of Greater Indianapolis stressed the need to think outside the box and to remain persistent, commenting that it takes her an average of three calls to get a participant to a DPP session, and even then her average conversion rate is 30%. She explained how her success is often dependent on the physician – if a clinician signs a prescription recommending the program, her conversion rate can be as high as 60%. Her best advice? Keep going until you hear, “do not call me anymore.” A major theme from the panel was the need for a structured protocol that still allows for a tailored approach to lifestyle modification. We left the session feeling cautiously optimistic: Regardless of size and structure, by remaining creative and open to innovative solutions, the DPP has the capacity to substantially impact lives and to slowly-but-surely reduce type 2 diabetes prevalence and incidence.

Evaluation of CDC Investments to increase DSMES Access and Utilization: Lessons Learned from Work with State Health Departments, the American Association of Diabetes Educators, and the American Diabetes Association

Magon Saunders, MD (CDC, Atlanta, GA)

CDC’s Dr. Magon Saunders positioned DSME as a key puzzle piece in achieving the national goal of Healthy People 2020, but emphasized that it won’t have a meaningful impact on population-level health unless it’s targeted more aggressively to underserved rural areas. As the name suggests, Healthy People 2020 outlines disease-specific goals to accomplish in US public health by the year 2020. In diabetes, the essential goals are to reduce prevalence (listed as ~29 million people), to lower the burden of disease (diabetes is listed as the 7th leading cause of death), and to improve quality of life for all people with diabetes or at risk for diabetes (we love that prediabetes is incorporated into this initiative). When done right, diabetes self-management education (DSME) can reliably produce 1% A1c decline for engaged participants, according to Dr. Saunders. This enhanced glycemic control correlates with significantly improved outcomes, including a 21% risk reduction for all-cause death. With this impressive impact in mind, the CDC teamed-up with the ADA and AADE to establish DSME programs across all 50 states, to put payment/reimbursement mechanisms in place, and to market the programs so that more patients are referred to DSME by their primary care providers. As of 2016, >one million people with diabetes were enrolled in a certified DSME program, corresponding to a ~4% participation rate across the entire diabetes patient population. Ms. Saunders also shared that 62% of rural communities in the US do not have a DSME program. Moreover, whether or not a rural county has access to DSME is significantly correlated with diabetes prevalence in that area. She described rural populations as an “untapped group of people that need your help,” really encouraging educators to get involved in rural health efforts. Indeed, US maps show that diabetes is most concentrated in regions lacking access to high quality health services (which refers not only to hospitals or endo practices, but to psychosocial supports for chronic disease management, including DSME). Pockets of high diabetes prevalence/incidence line up with rural areas of the country. Dr. Saunders recognized cost as a tall hurdle, and as such, the CDC has charged all states to work to achieve Medicaid coverage of DSME. Since launch of the CDC/ADA/AADE collaboration, the number of Medicaid recipients being reimbursed for DSME has climbed steadily, surpassing 2.5 million by year no. 4. That said, there are 30 states that still don’t offer Medicaid coverage of DSME, and Dr. Saunders urged educators to petition for this. This was a brilliant and inspiring talk, reminding us of how powerful education and psychosocial supports can be in diabetes care, but also showing us how much work remains to be done in expanding patient access to these all-important services.

Psychology of Diabetes

Screening for Diabetes Distress and Depression: What Should the Diabetes Educator Do?

Mary de Groot, PhD (Indiana University School of Medicine, Indianapolis, IN)

Clinical psychologist Dr. Mary de Groot issued an impassioned call for greater psychological support for people with diabetes, highlighting the ADA’s 2017 Position Statement on Psychosocial Care as an important step in the right direction. She set the stage by calling attention to the connection between diabetes and depression, noting that as many as one in four people with diabetes will develop depression – twice the rate of the general population. Equally troubling is that 38%-45% of people with diabetes report moderate to high levels of diabetes distress, a condition characterized by loss of motivation for self-care behaviors and inability to maintain an intensive treatment regimen. Beyond taking a significant toll on mental well-being and quality of life, the impact of depression and distress in people with diabetes is worsened glycemic control, decreased adherence to medication, and greater severity of diabetes complications – leading to increased medical costs, greater functional disability, and elevated rates of premature all-cause mortality. The ADA’s Position Statement on Psychosocial Care, written in collaboration with the American Psychological Association (APA), marks an important first step in defining best practices, general recommendations, and future aspirations for how psychological care should be delivered within the context of diabetes management. Dr. de Groot hinted that a follow-up position statement (in development as we speak!) will delve deeper into issues of implementation, or how to see these recommendations through at a systemic level.

• According to Dr. de Groot (herself an author of the position statement), the core philosophy underlying this document is that psychosocial factors in diabetes exist along a continuum, ranging from adaptive/healthy behaviors to diagnosable behavioral health disorders. For instance, a patient’s attitude toward hypoglycemia could range from healthy awareness to a paralyzing fear that impedes optimal blood glucose management. Against this backdrop, the position statement outlines five key recommendations:
  
  • (i) Integrating psychosocial support into the medical care of all people with diabetes to improve both health outcomes and quality of life.
  • (ii) Regular screening for diabetes distress, depression, anxiety, disordered eating, and cognitive capacity.
  • (iii) Close monitoring of the performance of self-management behaviors as a window into psychosocial factors potentially affecting diabetes management.
  • (iv) Considering the patient’s life circumstances and incorporating this into diabetes management strategies.
  • (v) Addressing psychosocial issues immediately with follow-up from a behavioral health provider.
• Dr. de Groot emphasized that these recommendations are particularly important to consider at diabetes diagnosis, when the person is learning self-management practices, during transitions in the person’s life, at the onset of diabetes complications, and as the person ages. The document goes on to provide specific screening and treatment recommendations for some of the most common psychosocial issues in diabetes – depression, anxiety, disordered eating – and outlines the nuances of how these may be differently managed in children vs. adults.
• We couldn’t agree more that better psychosocial support is critical to improve diabetes care, especially in light of the reality that a majority of diabetes management is self-management. To this end, we were extremely pleased to see the position statement inspire broader conversations about the importance of psychosocial care. Most notably, the ADA’s globally-influential Standards of Care document is now updated to reflect a greater emphasis on psychosocial support, and ADA 2017, the largest diabetes conference of the year, placed an explicit focus on psychosocial care for the very first time. Though increased discussion on this topic is certainly welcome, we’re especially eager to observe a corresponding change in real-world clinical settings in the years to come. This will take some time, but Dr. de Groot emphasized that CDEs, as “the frontline diabetes care providers,” are uniquely well-positioned to turn the tide toward greater recognition of the psychosocial dimension of diabetes.

Why Words Matter in Diabetes Education

Jane Dickinson, PhD (Columbia University, New York, NY), Susan Guzman, PhD (Behavioral Diabetes Institute, San Diego, CA), Melinda Marynluk (Joslin Diabetes Center, Boston, MA)

The power trio of Dr. Jane K. Dickinson, Dr. Susan Guzman, and Ms. Melinda Maryniuk reprised their session on “why words matter” from ADA 2017 – but first, to illustrate that judgmental language persists in diabetes care, Dr. Dickinson shared an anecdote: She attended a dinner following this very session at ADA in San Diego where healthcare professionals were using the term “non-complaint” left, right, and sideways (this was so upsetting to hear, considering all the progress that seems to be happening on this front). The word “non-complaint” and its cousin “non-adherent” establish patient and provider as adversaries rather than team members, and they distill diabetes management into a task of following instructions rather than the whole-person experience of living with chronic disease. Dr. Dickinson discussed the label “diabetic,” the descriptors “control” and “uncontrolled,” and the idea of “suffering” from diabetes in the same vein – this language is judgmental and gets in the way of optimal diabetes care. During Q&A, one educator in the audience asked to add the adjective “obese” to this list of unacceptable language. Dr. Dickinson agreed that this label can be very harmful in the real world (as opposed to “person with obesity,” or simply stating an individual’s BMI), and she shared with some optimism that there is already published literature supporting the negative consequences of this stigmatizing adjective “obesity.” We were also reminded of the recent AACE position statement proposing an entirely new name for this medical condition: instead of “obesity,” “adiposity-based chronic disease” (ABCD). We’re excited about the potential for ABCD to combat stigma and unconscious bias, provided it takes root in medical schools and real clinical settings. Indeed, Dr. Dickinson argued that improving vocabulary in diabetes care is a no-brainer because it’s free, and easy enough. She speculated that language may be directly correlated with diabetes distress, and although there’s no empirical research on this to-date, she hopes to someday investigate and quantify the association. There is a formal paper on why words matter, supported jointly by the ADA and AADE, that will be published simultaneously in the Diabetes Educator and in Diabetes Care this December. But Dr. Dickinson, Dr. Guzman, and Ms. Maryniuk have a grander vision – they want to spread this message to a very wide audience (“as wide as possible!”), including healthcare professionals, the diabetes drug and device industries, the people behind digital health apps for diabetes, and the public media. We certainly see value to more consistency in how various stakeholders talk about diabetes, with all healthcare players adopting more patient-centric, non-stigmatized vocabulary. Ms. Maryniuk anchored this session with a rousing call-to-action: “You will all be our ambassadors to getting this message out there.”

What Skills Do I Use? A Sense Making Approach to Motivational Interviewing

Bruce A. Berger, PhD (Berger Consulting, Auburn, AL)

In a highly-interactive session, behavioral science expert Dr. Bruce Berger reviewed the principles of “motivational interviewing,” a patient-centric and non-judgmental health psychology technique he developed to address challenging cases of patient ambivalence and resistance to behavior change. Dr. Berger set the stage with an analogy: “We think we’re driving the bus and the patient is the passenger. Instead, the patient is driving the bus and we’re influencing the route.” To this end, the crux of motivational interviewing (or “MI”) is to help patients reason their way to the conclusion that they need to change their behavior in order to achieve their personal health goals – a strategy that runs completely counter to the traditional model of persuading patients to make such changes. Dr. Berger was careful to clarify that MI isn’t about motivating patients, but rather assessing their motivations – what’s keeping them from behavior change, and what would compel them to make changes? In his view, people who are resistant to healthful behavior change (i.e. starting a new medication, quitting smoking, exercising) are making sense of things (or “sense-making”) either incompletely or incorrectly. MI techniques therefore focus on precisely defining how exactly the patient is making sense of things (how do they understand diabetes, complications, medication, eating habits, etc.?), identifying the incorrect or missing information, and inviting the patient to reconsider whether this new information changes their sense-making. To illustrate these principles, Dr. Berger asked the audience to imagine a patient who thinks “I don’t know why I need this medicine, I feel fine.” While it may be tempting at this point for HCPs to launch into a discussion of how diabetes symptoms often don’t manifest but the disease has progressed to an advanced state, Dr. Berger warned the audience that this tendency dismisses the patient’s concerns and fails to address the underlying root of his/her resistance to taking medication – the notion that you can “feel fine” and still be at risk. MI instead recommends engaging in a conversation to better understand the patient’s perspective, leading with something to the effect of “you’re wondering why you really need this medication if you’re feeling fine” to assure the patient that you understand their hesitation, followed by an invitation for them to reconsider new information – something to the effect of “would you mind if I shared some thoughts with you and you let me know what you think?” We appreciated Dr. Berger’s incredibly actionable advice, and would certainly like to see greater use of MI strategies in diabetes care, where patients are especially susceptible to shame, blame, and scolding.

Program Active II: A Comparative Effectiveness Trial to Treat Major Depression in T2DM

Mary de Groot, PhD (Indiana University School of Medicine, Indianapolis, IN)

Dr. Mary de Groot overviewed results of the Program ACTIVE II study, a 12-week evaluation of exercise, talk/cognitive behavioral therapy, and a combination of the two as interventions for people with type 2 diabetes and comorbid clinical depression (n=140). The results demonstrate the efficacy of a combination of exercise and cognitive behavioral therapy for both resolving the symptoms of depression and lowering A1c – the latter of which is a new development from the original presentation of the study at ADA 2017. On psychological outcomes, all three interventions were associated with statistically significant improvements in depressive symptoms (p<0.05), diabetes distress (p<0.01), and quality of life (p<0.05) vs. usual care, and patients randomized to any of the three treatment arms reported fewer negative automatic thoughts (p<0.03 vs. usual care). These effects were sustained even after controlling for antidepressant medication use, which underscores the distinct benefit to exercise support (12 weeks with a personal trainer) and to talk/cognitive behavioral therapy (10 sessions over the course of 12 weeks). On diabetes outcomes, new data reveals that the combined intervention reduced A1c by an average of 1.3% in individuals with a starting A1c >7% (p=0.02). Neither intervention alone had a significant A1c-lowering effect. Excitingly, Dr. Groot alluded that six month data from the study will be released in the near-future, and a one year analysis is also planned. We look very forward to this, and are especially interested to learn whether these impressive results are durable over time. Notably, Program ACTIVE II enrolled adults from diverse income levels and educational backgrounds (each of which independently affects psychosocial health) in both urban and rural areas.  This underscores that not only are Program ACTIVE II tools effective in the treatment of comorbid diabetes and depression, they are also generalizable to a wide range of underserved areas in the US. These are important results given the relative scarcity of psychosocial resources for people with diabetes, who have approximately double the risk of depression compared to the general population.

#DSMA Twitter Chat

Cherise Shockley (DSMA), Hope Warshaw (AADE), Molly McElwee-Malloy (TypeZero), Mila Ferrer (Beyond Type 1), Scott Johnson (mySugr), Mark Heyman, MD (One Drop)

The day closed with a Roche-sponsored #DSMA (Diabetes Social Media Advocacy) Twitter chat, where we heard heartfelt insights on living with diabetes from an all-star panel of patient advocates, joined by members of the diabetes online community Tweeting in. Led by DSMA founder Ms. Cherise Shockley and featuring the AADE’s Ms. Hope Warshaw, TypeZero’s Ms. Molly McElwee-Malloy, Beyond Type 1’s Ms. Mila Ferrer, mySugr’s Mr. Scott Johnson, and One Drop’s Dr. Mark Heyman, the conversation focused heavily on the psychology of diabetes. Key themes included the too-often underappreciated issues of diabetes distress and depression, how to combat diabetes stigma, and how to improve the language surrounding diabetes. These #DSMA chats – typically hosted every Wednesday at 9pm ET – offer a powerful outlet for people with diabetes to have their voices heard and to know that they are not alone, and this chat was certainly no exception. The discussion left us even more eager for the start of the full AADE agenda, which promises to take an even deeper dive on these crucial issues in diabetes care. Below we include some of our favorite Quotable Quotes from the chat, from panelists and Tweeters alike:

• On psychosocial considerations of diabetes:
  
  • “Focus on quality of life. If quality of life is crap, we won’t be able to do anything. And just talking about one medication or one blood glucose won’t make my quality of life go round – ask me how I’m doing, but don’t ask me about a stupid fasting blood glucose. Talk to me like a person.” – Molly McElwee-Malloy
  • “As patients, we should take the time to educate providers on what’s going on in our heads. As healthcare providers, take the time to understand mental health issues. A1c, insulin dosing, whatever the issue is in diabetes, it comes down to psychosocial health.” – Dr. Mark Heyman
  • “I love that we’re talking about this. When I was fighting depression, I didn’t know about the link between diabetes and depression. And when you’re depressed, that’s a really shitty time to find out about this link. That’s a very late time to begin building your support network.” –  Scott Johnson“I had a CDE visit and the educator asked me about a 240 mg/dl blood glucose. I thought, ‘Oh no, I have to figure out a story here! Well, I had pizza the night before, and…’ I should’ve just said ‘Well, I have diabetes!’” – Dr. Mark Heyman
• On how to fight diabetes stigma:
  
  • “Help people feel ok saying ‘this is not a regimen I feel ok managing in my life.’ And really respect that. Meet each other as humans, and be really sensitive humans.” – Hope Warshaw
  • “As patients we need to be okay with saying that we’re not okay. We don’t want our healthcare provider to look at us like we’re doing something that we’re not supposed to do. It’s our responsibility to say this isn’t okay and let that suit of armor come off and be human. I think that’ll help the conversation.” – Cherise Shockley
  • “We need to feel your empathy. We need to feel that you know we’re working extremely hard and not every day works the same. We’re following instructions and troubleshooting, but sometimes it doesn’t work.” – Mila Ferrer
•  On language:
  
  • “There is a lot of work to do around how the media thinks about and talks about diabetes. First, of all, people with diabetes don’t ‘suffer.’” – Hope Warshaw
  • “Clearly, language matters in diabetes. It’s that simple.” – Cherise Shockley

Success Beyond A1c: How Social Support Networks Help Improve Diabetes Outcomes

Manny Hernandez (Livongo Health, Mountain View, CA), Jeff Hitchcock (Children with Diabetes, West Chester, OH), Anna Norton (DiabetesSisters, Chicago, IL), Lorena Drago (Hispanic Foodways, Forest Hills, NY), Mila Ferrer (Beyond Type 1, Orlando, FL)

In an inspiring panel moderated by owner of Hispanic Foodways Ms. Lorena Drago and co-founder of TuDiabetes and the Diabetes Hands Foundation, Mr. Manny Hernandez (now at Livongo), leaders in the field Jeff Hitchcock (Founder, Children with Diabetes), Mila Ferrer (Director of Programs, Beyond Type 1), and Anna Norton (CEO, DiabetesSisters) discussed the value of the diabetes online community. Right off the bat, it was clear that there is still much to be done in promoting the DOC – when Mr. Hernandez asked the audience to indicate whether they were familiar with the online community, only about a third raised their hands. Wow was that gap surprising, given the engaged educator crowd. Serving as a poignant argument for the necessity of the DOC, Mr. Hernandez showed his favorite image of the blue IDF circle with a small slice removed, representing the time in one year that patients actually interact with providers: only 0.007% on average. For the remaining 99.993% of the time, patients are tasked with managing diabetes on their own. All members of the panel emphatically urged providers to visit online communities to gain perspective and knowledge. They offered advice for engaging with patients online, and above all stressed the importance of peer support. We were particularly excited to hear Ms. Ferrer mention the upcoming AADE Core Concepts course in November, which will feature patient participation. See below for some of our favorite quotes from the session!

• Quotable Quotes
  
  • “I’ve had type one for 25 years, and I didn’t think I needed a peer support network until I realized that I did. Peer support is what allows me to be a wonderful patient advocate and figure out what other women are needing that live the same life I live.” – Anna Norton
  • “Life is lived off-label – never forget that. We have a tool chest of devices and drugs available to us, and we have to use them to achieve our goals. We share how we live well with what is available to us today.  Be prepared to see that – it might give you ideas.” – Jeff Hitchcock
  • “A person who is educated is an empowered patient. Social media and support is a great way to start for those families feeling lost.” – Mila Ferrer
  • “The DOC completes me as a provider because I am able to understand better, to serve better, to advocate better.” – Lorena Drago
  • “We have to learn how to adapt our diabetes to our lifestyle. I remember very clearly the 2 AM club where I would wake up to check my son’s blood sugar, and I could find other parents who were online and checking. If I talked to someone, another parent, we are talking diabetes, we know each other, we understand how that feels.” – Mila Ferrer
  • “Your diabetes may vary, but no matter what you are seeking, there is a support group somewhere online for those needs, so I encourage your patients to go online and find that support.” – Jeff Hitchcock
  • “You’re missing 99.993% of your patient’s lives if you’re not online. If you’re not there you can’t expect to make a difference.” – Jeff Hitchcock
  • [On rules of engagement for providers on the DOC]: “If we’ve come up with something innovative, we want validation because we’re doing this on our own. If we’re doing something dangerous, you should tell us for safety reasons.” – Anna Norton
  • “I want to see more providers engaging with us on social media, I want to see educators sitting with us and sharing with other educators what you have learned and the ways you perceive our lives with diabetes. We need more Hispanics, we need more Spanish. We have a very large Hispanic community living with diabetes, and we don’t have enough resources.” – Mila Ferrer
  • “As a provider, when you live in the community, you start to see what families are struggling with and what they’re not bringing to you. This can inform what you talk to them about when you see them.” – Jeff Hitchcock

Outcomes Beyond A1c

Health, Diabetes, and the Need to See Beyond A1c

Richard Wood (dQ&A, San Francisco, CA), Adam Brown (The diaTribe Foundation, San Francisco, CA)

dQ&A CEO Mr. Richard Wood gave an insightful presentation based on multiple patient surveys (n=5,000 total participants), emphasizing A1c’s inability to capture the holistic impact of diabetes on quality of life. Mr. Wood presented the compelling time-in-range data first shown at the August 2016 and July 2017 Outcomes Beyond A1c meetings! Today, he shared some fascinating additional cuts of those data and new results. The powerful, open-ended “Is your diabetes management better or worse this year than last year? And why?” question was particularly illuminating. Based on their paragraph responses, Mr. Wood concluded that A1c is not at the top of many patients’ checklists: Just 25% of type 1s, 20% of type 2s on insulin, and 25% of type 2s on oral medications mentioned A1c unprompted in their responses. What did they mention instead? Diet, weight, eating, exercise, cost, insurance, etc. (As an aside, the document with these open-ended responses should be required reading at diabetes companies – contact dQ&A for more details.) Mr. Wood called the panel data correlating time-in-range and quality of life “compelling.” The slide below shows that as self-reported time-in-range increased, emotional well-being improved – fewer people in the “low” well-being category and more in the “high” well-being category. (The Warwick-Edinburgh Mental Well-being scale is designed to put most people in the “average” bucket, which is why the middle category is so large in the slide below.) As previously presented, Mr. Wood also showed that people with diabetes ranked time-in-range as having the biggest impact on daily life (statistically #1 for type 1s and statistically tied with A1c for type 2s). Cue JDRF’s Dr. Aaron Kowalski from yesterday: “My life is not defined by a three-month average of glycated hemoglobin.”

• More granular questions from the surveys also helped explain why A1c came up so infrequently in patient responses. First, A1c improvement doesn’t always make the person with diabetes feel better, and it doesn’t guarantee emotional payoffs. Of those who reported their A1c was “worse” than last year, 22% called their diabetes care “successful” at limiting or preventing negative feelings. This rose only slightly to 35% in those reporting the “same” A1c as last year, and stayed at 35% for those reporting a “better” A1c than last year. In other words, improving A1c was not enough to improve perceived quality of life.  This common-sense statement is beautifully captured in Mr. Wood’s presentation – diabetes is a multifactorial disease that impacts life all over the map. Patients in the dQ&A panel reported detriments in the realms of relationships, finances, energy, sleep, physical ability, and stress, but were pleased with their support networks, spiritual lives, confidence social situations, etc. (the second slide below depicts stark differences between subsets of patients – as we would expect, those not on insulin appear to have relatively better qualities of life in the featured categories). We hope this data set nudges diabetes therapy manufacturers and providers to bring a more holistic lens  and drive responses onto the right side of the graph.
• Mr. Wood provided rationale behind dQ&A’s use of the Warwick-Edinburgh Mental Well-being Scale, noting that brevity is an important asset – “many instruments are too long.” The Warwick-Edinburgh scale is short, easy to take positively worded, validated in 14 countries and languages, covers both feeling and functioning, and is sensitive to changes that arise from programs that encourage activity and healthy eating. “In the last two weeks, on a scale of one to five, are you feeling optimistic about the future? Do you feel useful? Relaxed? Do you have energy to spare?” And so on. The only real con that Mr. Wood pointed out is that the scale is not diabetes specific. We love that he suggested any instrument at all and provided very specific rationale for using it – the field will hopefully start moving toward consensus for the purposes of regulatory decision-making and perhaps, one day, reimbursement. 

• Previous dQ&A data show that social stigma is still very much a barrier to emotional well-being: 20% of type 2s on oral agents, 30% of type 2s on insulin, and 40% (!) of type 1s “strongly agreed” that they have been made to feel guilt, shame, isolation or blame because of their diabetes. As Dr. Kowalski noted yesterday, stigma can preclude people from leveraging therapies that could otherwise be very beneficial. This is a major issue, and one that we hope more discreet and user-friendly products will help address.
  
  • The stigma divide between type 1s and type 2s is marked and needs to be closed. Mr. Wood presented very interesting data examining the dissonance between what patients say and what they do, with respect to social stigma. As can be seen in the image below, a majority of type 1s in the dQ&A panel said that diabetes comes with a stigma attached, yet they reported being mostly open about it on Facebook; on the contrary, a majority of type 2s say there is no stigma attached to diabetes, yet few reported that their Facebook friends know they have it. We found this both fascinating and unfortunate – we were glad to hear numerous times at this meeting the sentiment that diabetes is diabetes, everyone’s diabetes is different, and neither type 1 not type 2 is the patient’s fault.
  • The dQ&A data on stigma was published in Clinical Diabetes earlier this year – see the publication here.

Our own Adam Brown (stepping in for Kelly Close, who had an unexpected family emergency during AADE that kept her from Indy) discussed outcomes beyond A1c, including: recent consensus progress from July 21; personal examples of time-in-range -> emotional well-being (“Glucose is a means to an end, not the end itself”); and his speculation on how care might evolve in a beyond-A1c, technology-driven era. Download his slides here.

• Why do outcomes beyond A1c really matter, according to Adam? “Glucose is a means to an end, not the end itself.” Amen! He showed several slides with screengrabs of his personal CGM traces, and explained the world of difference that being in range makes (the slides below pretty much sum it up). When he is in range, he (and Kelly) call it “my best self” – he feels well-rested, productive, energetic to enjoy life, in the moment, calm, low stress, and feels that diabetes is in the background (what should be one of the ultimate goals of a therapy). He told a story of waking up at a high glucose, taking a “rage bolus,” crashing low on a walk to a work event, getting all sweaty, feeling embarrassed, treating the low, feeling exhausted, and having his whole day negatively affected. While his average glucose for the day looked fine, the quality of life impact was not captured. The beauty of CGM, he said, is that we can measure glucose levels paired with quality of life measurements in real-time – we would hope to see a study of this nature funded, leveraging some of the experience-sampling methods that happiness researchers have used for years. Ultimately, if we could connect time-in-range, hypoglycemia, and hyperglycemia to significantly impaired quality of life – in the moment, prospectively – it could be very compelling data. Perhaps it would be a good way to “validate” time-in-range and CGM outcomes …

• What would a Beyond-A1c appointment look like? The word web in the slide below, shows a conclusion from Adam’s talk – as technology improves with connected devices and algorithms, educators will (hopefully) spend far less time on downloading data and sorting through numbers, and far more time on quality of life, motivation, barriers to behavior change, motional interviewing, and emotional well-being. Specifically, Adam suggested educators should expect to: (i) have richer access to data (CGM, pump, smart pen) and more automatic decision support – similar to IBM Watson’s capabilities in oncology. For examples of diabetes decision support, he mentioned insulin dose titration, a talk from ADA on diabetes treatment optimization based on big data, DreaMed’s Advisor Pro, and Medtronic/IBM Watson’s Sugar.IQ. (ii) Focus more on emotional well-being and less on the numbers. (iii) Move from face-to-face to remote, more continuous communication (text, chat, video); and (iv) leverage new tools for education: voice, virtual and augmented reality – “imagine the day when Amazon Alexa educates patients. ‘What should I eat for breakfast today based on my previous patterns, Alexa?’” (The audience seemed impressed by the thought of this). His point was that computers are great at analyzing heaps of data, and people are good at connecting with other people. This sort of decision support (some of which is already here), should hopefully free up educators’ time to focus on what impacts quality of life for people with diabetes, besides glucose. Ideally, algorithms will take care of driving glycemic improvements, and healthcare providers can focus on the human aspects and more nuanced scenarios.

 

• Adam kicked off his talk by explaining the limitations of A1c and updating attendees on the progress made toward consensus on outcomes beyond A1c (see our report on the July 21^st Glycemic Outcomes Beyond A1c meeting). He began by displaying a quote that puts into context the challenge of measuring diabetes based on an average: “If I stand with one foot in a bucket of ice water and one foot in a bucket of boiling water, on average, I am comfortable.” He also pointed to data from Drs. Irl Hirsch and Robert Ratner, as well as Drs. Rich Bergenstal and Roy Beck (“The Fallacy of Average”) to note limitations with A1c – many factors influence it (an estimated 14%-25% of A1c measurements in a typical practice are misleading, according to Dr. Hirsch), and a wide range of glucose values could translate to a given A1c (e.g., an A1c of 8% could correspond to a mean glucose of 147, 180, or even 217 mg/dl). Fortunately, the field is making strides: at the recent July 21 Consensus meeting in DC , representatives from JDRF, AACE, Endocrine Society, ADA, ATTD, and the International Hypoglycemia Study Group agreed on the glycemic “bins” that should be measured (see slide below), that CGM should be used in clinical trials, that coefficient of variation is the best metric for glycemic variability, that two weeks of data is sufficient to evaluate a glycemic profile, and that the AGP should be the “EKG of diabetes.” Stay tuned, this is certainly not the end of the conversation!

Questions and Answers

Q: A lady, a patient of mine, said her A1c was 7.9%, but she had frequent low lows and high highs. But her doctor was happy because of her “good” A1c!

Adam: Yes, it’s a great point. Physicians are often ranked and paid based on A1c, and that’s a problem. We can only change that with better data on why time-in-range, hypoglycemia, and hyperglycemia matters for patients’ health.

Dr. David Marrero: And just to be clear: let’s not throw A1c completely under bus. It illuminates people who are chronically high. We don’t want to ignore it, but we also don’t want to over-emphasize it.

Dr. Michelle Litchman: When will time-in-range have benchmarks? How does it apply for those without CGM?

Adam: Yes, this is the next question – what should time-in-range actually be? I’ve heard some people in the closed-loop community mention 70%+ time in 70-180 mg/dl as a benchmark, but there is definitely not agreement on this. Keep in mind – the field just agreed on what the time-in-range threshold should even be. From here, I think many would like to see benchmarks. I think we need to look at the data and see where the inflection point is between a certain time-in-range and outcomes.  

Dr. Marrero: It is a data question, but until you see a relationship to outcomes, it’s hard to see when that’s going to happen. Access to CGM is still a huge issue, and in my part of the country [Arizona], you cannot get it. My Latino and Native American brothers and sisters can’t get this. it took the DCCT to promote intensive insulin management. Glucose monitoring has gotten way better, but it’s not perfect yet – still a lot of error. It won’t be worked out next week, but it will happen. Until you show me data linked to better outcomes, it’s going to be damn hard to get it paid for.

Adam: And in terms of people on fingersticks and those with type 2 diabetes, we also need to show outcomes and better data that CGM works. It will take time, but I’m an optimist about CGM in type 2 diabetes.

Dr. Marrero: FDA is now incorporating patient-reported outcomes as part of its review process. That’s happening now, and they’ve gotten pretty adaptive. A year from now, as trials progress, you’ll see those as part of regulatory review.

Diabetes Outcomes Beyond A1c: Time in Range and Beyond

Aaron Kowalski, PhD (JDRF, New York, NY)

The great Dr. Aaron Kowalski (JDRF), a key voice in the outcomes beyond A1c movement, gave a most valuable talk on diabetes outcomes metrics and the tradeoffs between diabetes happiness (quality of life) and diabetes health.

• “The holy grail goal of treatment is to restore the person to a state where they were before diabetes, and to let them worry about other stuff in their lives without diabetes in the background. My life is not defined by a three-month average of glycated hemoglobin ... it’s just not.” Dr. Kowalski made a number of arguments against the use of A1c as the primary diabetes outcome metric upon which therapies are evaluated. Data from the just-published “The Fallacy of Average,” for instance, shows that a mean blood glucose 0f 183 mg/dl could correspond to an A1c of anywhere between 7%-9%. “This really sums it up for me – this is not the perfect end-all, be-all metric.” He put forth valuable points on A1c’s unreliability in certain clinical scenarios (genetic variation, racial differences), and also provided the less-common argument that glycation is an irreversible process – spending time in hypoglycemia does not reverse the rate at which hemoglobin is glycated. Dr. Kowalski noted that hypoglycemia is obviously the most relevant short-term complication of diabetes, yet A1c does not capture it – “if it weren’t for hypoglycemia, we wouldn’t be here. You’d just dose more insulin!”
  
  • Dr. Kowalski called for the consideration of metrics that evaluate time-in-range, DKA, severe hypoglycemia, psychosocial issues (“tremendously under-appreciated”), and weight, among others. “We need payers to approve stuff based on hypoglycemia reduction, based on sleep improvement, and based on other things that matter to people living with diabetes.”
  • The benchmark time-in-range (70-180 mg/dl) in Dr. Kowalski’s mind? “More!” We like this approach – as long as a therapy increases time-in-range, than it is helping someone with diabetes do better. That said, we assume FDA and payers may need more granularity than this, since it will help with benefit-risk calculations and cost-benefit analyses – what is a meaningful improvement in time-in-range? For a point of reference, patients using the MiniMed 670G hybrid closed loop are spending ~70% in-range (70-180), which some KOLs like Dr. Rich Bergenstal have suggested is a possible baseline benchmark. Dr. Kowalski noted that capturing time-in-range is CGM-dependent, but he hearkened back to Dr. Roy Beck’s excellent Keystone talk, indicate that CGM systems are more accurate than many fingerstick meters. DTS’ BGM Surveillance Program corroborates this point – two thirds of meters tested didn’t meet the ±15%/15 mg/dl accuracy threshold 95%+ of the time.
• Dr. Kowalski called attention to the high level of burden conferred by many of today’s (and especially yesteryears’) advanced technologies. “Wearing a pump, poking yourself six times a day, these are things that people would never do if they didn’t have diabetes. They are true barriers to doing better.” Dr. Kowalski turned to CGM: “The fact to me that one in five type 1s in the T1D Exchange wears a CGM is shameful. How is that possible? Well that’s easy for me to say. For a teenager … there are barriers like skin reactions, visibility, stigma. These tradeoffs impact decisions. I’m a huge believer that everyone should be collecting glucose all the time, but this doesn’t match the lives of every person. When you’re at the beach, not everyone is wearing a CGM or a pump, that’s a potential barrier. Or skin irritation. Or alarming at school or work. With CGM, we’re seeing a tipping point go over where more people seeing value, but we’re not all the way there yet.” Some barriers are certainly being diminished through better products – less clunky form factors, factory calibration, data on the watch or phone app, etc. – and others are quite addressable like awareness, clinical inertia, baggage from prior generations, etc. We are optimistic that adoption will continue to rise, but a very big barrier to adoption is still cost (Tanenbaum et al., Diabetes Care 2017) – and related to it, prior authorizations, documentation hassles, and the administrative demands of prescribing and staying on CGM.
  
  • Dr. Kowalski on the Achilles heel of pump therapy, the infusion set: “Gosh this is a no brainer area for innovation. It’s a pain, time consuming, and garbage-making. It’s awful, and we’ve got to do better.” Dr. Kowalski said that someone videotaped a set change and counted 60 distinct steps involved. He believes that if this process were simpler, it’d be easier to get more people on pumps, and he has been begging companies to work on this. He hopes that the BD/Medtronic MiniMed Pro infusion set will be back on the market soon (set to resume launch in FY18, per the recent update), and that Convatec/Unomedical continue to innovate.
• Dr. Kowalski and Dr. David Marrero both chimed in (in separate sessions) on glycemic variability as a metric that should be validated and used to assess diabetes therapy. Dr. Kowalski said that he and Dr. Irl Hirsch debate all the time about the link between glycemic variability and long-term complications. Existing literature has yet to identify a correlation – and a controversial Diabetes Care publication from April says there was none between within-day glycemic variability and microvascular complications in the DCCT (beyond mean glucose). We’d note that these studies aren’t nearly equipped to answer this question, because they didn’t include CGM data. Dr. Kowalski approaches the issue from a logic standpoint: “high blood sugar is bad, low blood sugar is bad, if you’re swinging between them, it’s bad.” Indeed, if stakeholders can be convinced that high and low blood glucose levels are both bad, then low glycemic variability or time-in-range (with an acceptable mean glucose) should be a good indicator of outcomes. Then again, as Prof. Phillip Home said at the July 21^st meeting at FDA, “I think it, but that’s not the same as convincing someone else.” FDA and payers may require further evidence from either an RCT or observational data that low glycemic variability (or high time-in-range) is linked to lower complications risk. To be honest, we think the link between diminished quality of life and time-in-range is far easier to validate and could be quite impactful.
  
  • Dr. Marrero took a different perspective on the issue: “My hypothesis is if you’re going up and down, you feel like crap, and if you smooth out you feel better.” We wonder if the right prospective data could show this, if payers would pay for therapies on this basis – we suspect that the answer is no but that they would pay if associated with fewer long term complications. The ultimate goal of any healthcare system, in our view, is to offer citizens long and happy lives. How should the latter be measured in diabetes? Could CGM help, assuming time-in-range and out-of-range are linked directly to poorer quality of life?
• As at Keystone, Dr. Kowalski expressed relief (and frustration) that CMS finally decided to cover therapeutic CGM, calling it “absolutely bananas” that it took this long to achieve. He was delighted that we’ve finally gotten over this major hump, and expects it will drive better outcomes for a population of adults who may be at higher risk for hypoglycemia-related injuries.
  
  • On healthcare in general, Dr. Kowalski noted that we’re in an environment that is challenging for people with diabetes. He closed out this microcosm of his talk to claps after asserting that we can’t have people making life decisions because they can’t afford their insulin.

Health, Diabetes, and the Need to See Beyond A1c

David Marrero, PhD (University of Arizona, Tucson, AZ)

In a rather personal address, University of Arizona’s Dr. David Marrero explored the importance and complexities underlying health-related quality of life (HRQOL) as it pertains to diabetes. He began by reminding attendees the definition of HRQOL – personal or emotional well-being as a function of diabetes and its treatment. Unsurprisingly, HRQOL decreases with disease progression and onset of complications, but that’s where the simplicity ends. For one, HRQOL is an issue of context, meaning that it is dynamic – people with diabetes have different experiences of quality of life depending on the scenario – and it has multiple dimensions. Diabetes doesn’t only impact glycemia, but other factors such as physical functioning, cognitive aptitude, social life, etc. Further, Dr. Marrero pointed out, diabetes can yield both positive and negative outcomes on one’s life. While the “crap” is all too-often discussed, the “flowers” (e.g., healthier eating, proficiency with conceptualizing time and numbers) are frequently overlooked. And lastly, HRQOL domain measures are often unrelated to behavioral aspects of self-management or A1c – a treatment may have excellent therapeutic efficacy, but not result in improvements in, or even diminish, quality of life. (Similar to Dr. Aaron Kowalski’s “diabetes happiness” (quality of life) vs. “diabetes health” teeter-totter.) For instance, both Dr. Marrero and Ms. Virginia Valentine agreed that Symlin (pramlintide) does wonders to blunt postprandial spikes, but because it didn’t move the “holy grail” that is A1c, it’s now “a pain in the butt to get” (higher cost, prior authorizations necessary). Dr. Marrero did cite this treatment satisfaction study on pramlintide, published in Diabetes Care in 2007 – we wonder what could be learned here for labeling drugs in the future. Dr. Marrero invited attendees to enter a deal: “A1c is a measure of glucose. That’s all it is boys and girls, not how I’m doing with my life, my wife, my job. Let’s move away from looking only at A1c and move to seeing how people are doing with their diabetes holistically.” Yes!

• Dr. Marrero didn’t provide specific recommendations for instruments to measure HRQOL in his talk, but that’s largely because, as we understand it, the field still needs some consensus here. Instead, Dr. Marrero suggested a number of guidelines/questions to ask as a clinician sets out to evaluate HRQOL: (i) What are you trying to accomplish?; (ii) In what ways will the participant be affected?; (iii) Distinguish between patient-reported outcomes in general and quality of life specifically. “Ask me if I have pain, that can have nothing to do inherently with quality of life.” Dr. Marrero, for example, had shoulder surgery three weeks prior to the talk. He reported that he can manage the pain fine, but it is a hassle to take off his coat – he requires assistance, which can be difficult when he is alone and even a bit embarrassing. This may or may not be captured, depending on the question asked. (iv) Avoid using components of composite measure – you must interpret the whole measure, or else it is not valid; (v) Consider the impact of an intervention on quality of life of other close family members and caregivers (“the first time I got a CGM and started alarming at three, four in the morning, guess who wasn’t happy?”). (vi) Timing of assessment – the changes in quality of life don’t necessarily follow the same trajectory as changes in behavior or A1c.
  
  • To an audience member who asked for advice on a validated instrument, Dr. Marrero responded that “there’s a lot of stuff out there. You can find stuff that works for you, and if you can’t, use logic and make up your own.” We certainly appreciate the magnitude of literature on this topic, and we hope to see the field approach some consensus with respect to that instruments should be used. Only then will comparisons be possible and measures can be used for regulatory decision making (and perhaps one day, provide useful data for reimbursement).
• Dr. Marrero shared a fascinating anecdote from his thesis, entitled Adjusting to Misfortune. At the time when he was diagnosed (40 years ago, this September), there was very little literature on HRQOL, especially around diabetes. “Kids at the time were going into DKA and were in the hospital every two weeks, and the consensus was that they were little shits, non-compliant, so what did you do after DKA in the hospital? More education.” Dr. Marrero studied these kids over time, interviewing them and visiting their homes to figure out why they were going to the hospital so frequently. He recalled an instance where he visited a boy’s house, only to find out that the family lived in squalor – they were hoarders. As he was departing the home, it hit Dr. Marrero that the boy went to the hospital to escape – replied the boy, “that’s the only time I have clean sheets and three square meals a day.” This anecdote illustrates, in a nutshell, the complexities of diabetes – it’s more than adjusting insulin and following a doctor’s orders, and has a lot to do with perspective and what else is happening in life. The boy was doing something adaptive for himself, but maladaptive by healthcare provider standards. Of course, none of the educators in the room were surprised to hear this anecdote.
• Dr. Marrero had just returned from the American Psychological Association’s 2017 meeting, where he administered the second leg of the new ADA/APA mental health provider diabetes education program (supported by Helmsley Charitable Trust). He leads the very important initiative that strives to familiarize more mental health professionals with the specific needs of people with diabetes – for this, we are so grateful.

Hypoglycemia Safety Initiative: Choosing Wisely for the Wise Diabetes Educator

Sharon Watts (US Department of Veteran Affairs, Washington, D.C.)

Ms. Sharon Watts, a VA nurse practitioner who helped administer the ACCORD trial, argued against a stringent guideline that A1cs should be <7%. She pointed out that the evidence often-cited to support keeping A1c under 7% to prevent complications is from the UKPDS study, which (in her view) is not generalizable. The participants in UKPDS were newly diagnosed type 2s with median age of 54 years – “this is not the 86-year-old patient that comes walking into your office with a duration of 20 years.” Further, she said the A1c of <7% obtained in this trial was only sustained for 4.5 years. (On the other hand, we’d point out the outcomes still showed benefit for <7%; imagine how much better they would be with stronger durability.) In the DCCT, she added, patients didn’t even achieve an A1c <7%. “We live in an age of evidence-based practice; where is the evidence for an A1c of <7%? The evidence isn’t really there. Just saying.”  For example, if presented with a patient with a “challenged heart” and many years of diabetes, Ms. Watts would rarely, if ever, recommend an A1c of less than 7%. In general, she posited that tight control is ok for young patients, but not the elderly. This assertion is apparently backed by recommendations from the American Geriatric Society in 2011: “Avoid using medications to achieve hemoglobin A1c <7.5% in most adults age 65 or older; moderate control is generally better.” We felt this talk was overly dismissive of two landmark outcomes trials in diabetes, and leads to a never-ending black hole that “we need more data” until we recommend lower A1c’s. Same believe hypoglycemia was a driver of the ACCORD finding, and with newer glycemic-dependent therapies that don’t cause hypoglycemia (GLP-1, SGLT-2s), we’re living in a different world than ACCORD. She is right that A1c targets should be tailored, but we should also be mindful of the message that raising the A1c target sends. 

• One woman in the audience commented that a lot of older patients with type 1 diabetes have been in many trials where a do-or-die mentality for A1c <7% has been drilled into them, and they are hesitant to relax their therapy. Ms. Sandra Hedin shared interim results from the pilot of the VA’s Choosing Wisely Safety Initiative (aiming to identify those at risk for hypoglycemia and relax therapy): Of the over 9,300 patients evaluated so far, hypoglycemia has been reported in 25%. Of those patients reporting hypoglycemia, 56% have made a shared decision with a provider to relax treatment. The program uses a complex, integrated approach. It first identifies a high-risk cohort (A1c<7%; on insulin or sulfonylurea; older than 75 with dementia/cognitive impairment or SCr>1.7 mg/dl) and sets out to convince them that there is such thing as an A1c that is too low through multi-disciplinary education, EMR tools (that identify in real-time patients that are at-risk), and online panel reports. We look forward to learning more and hope CGM can be optimally deployed in these investigations – there is no way to comprehensively capture hypoglycemia with just fingersticks. We like the idea of EMR incorporation and real-time risk monitoring, ideally automatically.
• VA dietician Ms. Mary Julius discussed the disconcerting link between food-insecurity and hypoglycemia. The graph below (from Seligman et al, 2014, Health Affairs) is extremely troubling: By the third and fourth weeks of every month, across the US, hospital-admissions for hypoglycemia increase, but only in low-income patients. This, together with data from the ACCORD trial (in which the number one cause of serious hypoglycemia was food-related – either delayed/missed meal or too few carbohydrates), suggests that we are not providing enough budget-friendly nutrition information to low-income patients. Ms. Julius urged educators to ask patients if, in the past month, there was ever a day when they went hungry because there was no money for food. Food insecurity, she added, is more prevalent in households including a person with diabetes. With all of the advanced technologies and drugs we have today to manage diabetes, we find it unacceptable for a lack of food to be the reason for severe hypoglycemia – there needs to be more done on the fronts of education and policy to make sure the curve in the chart below is normalized. We’d also note that food policy needs to change, since lower-carb options are often more expensive and high-carb/sugary junk food is often cheap. The latter comes with big needed insulin doses, which inevitably lead to big errors.

Additional Topics

An Engaging Panel of Key Industry Thought Leaders

Adam Brown (The diaTribe Foundation, San Francisco, CA), Dr. Ann Albright, PhD (CDC, Atlanta, GA), Virginia Valentine (Health Scripts Care, Albuquerque, NM), Mr. David Weingard (Fit4D, New York, NY)

In a keynote panel moderated by Ms. Virginia Valentine, Fit4D’s Mr. David Weingard, CDC’s Dr. Ann Albright, and our own Adam Brown discussed developments in diabetes care and the role educators will play in shaping its future. Mr. Weingard – who has ~100 CDEs on board at Fit4D – emphasized the need to remember cultural and social structural factors in diabetes. In a memorable example, he asked the audience to consider a Latino living in New York City as compared to a farmer in Nebraska – these two individuals have completely different barriers and even schedules. The farmer, he noted, is working in the fields during long hours in the summer, so educators will miss him if they call at the same time as a New Yorker. Dr. Albright emphasized translational medicine (“It’s great that we have publications and we must do that, but it means diddly if we don’t get that into people’s hands and improve their outcomes”) and stressed that interdisciplinary efforts are increasingly needed in the field. Mr. Brown highlighted the accelerating world of diabetes technology, sharing excitement for CGM’s growing adoption (though more work needs to be done on cost) and noting some FDA clearance momentum for insulin dose titration apps (Voluntis’ Insulia, Sanofi’s My Dose Coach, Amalgam’s iSage Rx, Lilly’s Go Dose).

• A topic that weighed heavily on all panel members’ minds was the increasingly over-burdened nature of our healthcare system. Dr. Albright in particular was adamant that key partnerships will have to be implemented to reach communities in need. Letting local communities take ownership over efforts and craft solutions is ideal, she emphasized; more buy-in at the start translates to greater program accountability and success. Both Mr. Weingard and Mr. Brown detailed the ways in which technology will hopefully ease provider burden, free up time currently wasted on data acquisition/analysis, and scale the reach of providers. Nearly all panel members also mentioned the burden of prediabetes– 84 million in the US as of the CDC’s just-published 2017 Diabetes Statistics Fact Sheet. We desperately need more providers, and Ms. Valentine encouraged educators in the audience to go for degrees like NPs, PAs, etc. “Primary care is drowing,” she noted. As Dr. Albright mentioned during her pre-conference presentation on the DPP, the numbers cannot continue to grow at their current rate – our healthcare system simply cannot handle it.
• Quotable Quotes
  
  • On Technology in Diabetes Care
    • “We use tech to help diabetes educators scale their reach. Diabetes is a job that no one wants, and we need to be able to encourage people, even just to download an app and learn to use it.” – Mr. Weingard
    • “It’s my full-time job to follow diabetes technology, and even I have trouble keeping up! So don’t worry if you are feeling overwhelmed by the pace of things – that’s the standard now. It does mean you’re going to get better tools. The thing I’ve seen a lot of progress on recently is CGM increasingly becoming the standard of care. We still have a while to go until its inexpensive for type 2s, but we’re getting to a point where everyone on insulin should be getting on CGM. It gives people with diabetes their own accelerated learning curve.” – Mr. Brown
    • “I think one thing we’re seeing a lot of are FDA cleared apps that can titrate insulin, so HCPs can set it up and prescribe it. Then, the app recommends dose changes as patients enter information. I think we’ll see those cleared for basal-bolus users too. They only use fingerstick data right now, but I think they’ll also move into CGM. Then, educators can focus on other things that matter – what are your barriers and what’s challenging you right now?” – Mr. Brown
    • “There’s a limited number of diabetes educators...The more comfortable you are with the tech, and can integrate it into coaching with patients, the more you’re able to leverage the best parts of both worlds – emerging technology and contact with patients.” – Mr. Weingard
    • “We must start with the premise that technology will become more important over time – there aren’t enough providers to deal with all the patients out there. I would recommend engaging more with technology, meaning testing out apps yourself, wearing devices, talking to companies, grilling them on what they are and how good they are, etc. Read diaTribe,org if you don’t subscribe. We’ll send you an email every 2 weeks. We just care about helping educators and patients.” – Mr. Brown
  • On Value-Based Care
    • “The reality is that primary care practices are being measured on quality – that they don’t have time to achieve –and the more all of you can help them achieve quality, and show them how you’ve changed the quality measures in the practice, the more you should be paid.” – Mr. Weingard
    • “In a preconference prediabetes workshop, I heard one attendee say the woman behind her said, ‘Oh, I’m not going to get into this because you get paid based on outcomes, and what if you don’t meet the goal and get CDC recognition?’ I totally understand that and why that was scary and problematic, but it’s important to remind folks that’s where we are and where we are headed in this country. Payers are paying for outcomes, not the process of going through something.” – Dr. Albright
    • “I personally don’t believe the patients should be paying for coaching and the way DPP is set up, pharma or payers that have the most to gain financially will invest in this because it’s a gain financially and socially. Remember the patient has enough to deal with. It’s a job they don’t want, so the easier we can make it for them to have contact with the educator, the better. We work with a lot of underserved communities, and we really have to take into account the access to the food and their resources.” – Mr. Weingard
  • On Changing the Face of Diabetes Care
    • “Our focus at the CDC is three things: prevent diabetes, prevent the complications and disability from diabetes, and eliminate diabetes related disparities. Right now, prevention is a major focus. For the first time in history, we’re building an infrastructure for lifestyle in this country, and diabetes is leading the way.” – Dr. Albright
    • “You know what’s going on in your communities. Please utilize the CDC state level data available to you, and use that data to help tell your story. Please tell stories about the patients you see. This is the winning combo: have evidence, describe the problem, describe the evidence behind the problem, and tell a story about someone whose life is impacted by it.” – Dr. Albright
    • “There’s an increasing recognition that we have to be able to reach different areas – Appalachia, rural, frontier, reservations – we can’t all get to those places physically and we do have to equip ourselves for that. It means we’re striking out new partnerships with companies around broadband, and we’re doing that more focused work at the CDC. It’s also about forming partnerships, and making sure people in those communities are helping to shape and build it. If you’re involved in shaping it, you’re more likely to engage and accept it.” – Dr. Albright
    • “Not everyone needs to run out and go to NP or PA school or pharma, but a lot of you do. Primary care is drowning, and I know you all know that. They love having you but we need to infiltrate the ranks, take your CDE into primary care practices, become a provider. Think about taking the next step because we all know primary care is facing this avalanche of people with type 2 and they really are overwhelmed.” – Ms. Valentine
    • “We need everyone. How many people with pre-diabetes? 84 million. I think we have plenty for everybody to do. We are incredibly committed to self-management education, and the CDC has invested with ADA and AADE in expanding it.” – Dr. Albright
    • “The research and the implementation science – that’s what the CDC does. We take the randomized trial and make it real for people. Some of them are really a foot in the door and there’s a step based on what people knew at the time. The challenge is the refinement of those measures going forward, which is why we all need to speak up and know the evidence and articulate the evidence in a way that makes sense to policy members.” – Dr. Albright

Proof that Diabetes Educators Do It Better: Supporting Persons with Diabetes

Julie Gee, PhD (Weber State University, Ogden, UT)

Dr. Julie Gee presented original research to demonstrate the critical role that diabetes educators play in patient-centric care, where the healthcare professional functions to empower patients to engage in their own health and to effectively manage their diabetes. Via an online survey sent to a database of AADE-accredited CDEs (n=225, which corresponds to a 30% response rate, fairly high for a survey), Dr. Gee’s team collected data on beliefs related to the idea of patients as “self-managers” (as measured by the Clinician Support for Patient Activation Measure [CS-PAM] scale) and on how extensively diabetes educators employ strategies to foster self-management (as measured by the Clinician Self-Management Scale). The study population of CDEs scored remarkably highly on both scales, indicating strong belief in the importance of self-management paired with a strong tendency to support self-management in their practice. In the domain of activating and inspiring patients to take on the role of self-manager, the study population exhibited an average CS-PAM score of 77.7 out of 100 – the highest seen in the literature to-date among any healthcare specialty, according to Dr. Gee (we think this is very impressive). This CS-PAM score translates to endorsement of ideas like “Patients should want to be involved as a full partner with me in making decisions about their care” and “Patients should know what each of their prescribed medications is for.” In terms of clinical practice to support self-management, the study population scored an average of 4.3 out of 5 on the Clinician Self-Management Scale – also very high. This translates to high levels of agreement with statements like “Tell the patient you will be their coach, but that they are the one who has to carry out the plan” or “Ask the patient what change s/he wants to focus on.” There were no significant differences in CS-PAM or Clinician Self-Management Scale scores according to CDE’s age, years of experience, or discipline (registered nurse, dietician, pharmacist, etc.) Moreover, Dr. Gee’s research revealed a significant correlation between CS-PAM score and Clinician Self-Management Scale score, indicating that the more favorably CDEs view self-management practices, the more likely they are to adopt clinical strategies that promote this. These findings exemplify CDEs’ leadership in the ongoing movement toward less paternalistic care that instead invites the patient to be a shared decision-maker. “Basically, CDEs rock – that’s what I found,” Dr. Gee concluded, hence her creative talk title, “Proof That Diabetes Educators Do It Better.” Hear, hear! We sincerely hope that Dr. Gee’s findings help underscore the absolutely critical work of diabetes educators, some of the most patient-empowering members of the care system. The need for increased awareness of CDEs’ work was illustrated best by one audience member, who remarked during Q&A: “We’re changing lives, but nobody knows that and nobody values us. CDEs are being scrapped in many health centers. We need to promote this information and educate everyone out there about who we are.” This was met with a standing ovation – one hugely deserved!

Gut Check: The Microbiota’s Role in Obesity and Diabetes

Meghan Jardine (Physicians Committee for Responsible Medicine, Dallas, TX)

Dietician and CDE Ms. Meghan Jardine delivered an informative and humorous overview of the gut microbiome to a packed (standing room only!) lecture hall (despite it being AADE’s very last session!), offering actionable strategies for how to promote microbiome health in the context of diabetes and obesity. Ms. Jardine’s microbiome presentation at last year’s AADE was equally popular, and it’s our sense that this is becoming a fan favorite! Ms. Jardine began her presentation with a review of the existing literature on the role of the microbiota in diabetes and obesity, outlining the prevailing hypothesized mechanism by which the microbiome influences metabolism. She explained that individuals who are insulin-resistant or obese exhibit a distinctive bacterial profile, characterized by reduced genetic diversity, a higher phylum-level ratio of Firmicutes to Bacteroidetes bacteria, and an increase in bacterial species like E. coli and Staphylococcus, which enhance inflammation. This pro-inflammatory microbiota phenotype is believed to increase gut permeability (an issue that is exacerbated by a high fat diet), which leads to increased fatty acid storage in adipose tissue, increased caloric harvest, and eventually increased insulin resistance and metabolic dysfunction. Precise microbiome-based therapies and diagnostics for diabetes and obesity remain far off, but Ms. Jardine overviewed an abundance of evidence pointing to the importance of existing diabetes management techniques – namely nutrition and exercise – in maintaining a healthy microbiome.

• Nutritional intervention, Ms. Jardine emphasized, is one very feasible way to overcome this vicious cycle; several studies in the literature show a causal link between diet and microbiome composition. Most notably, the well-known “diet switch” Nature study illustrates the flexibility of the microbiome according to an individual’s diet (as opposed to genetics). The study enrolled volunteers from rural Africa and the United States, investigating the effects of reversing the high-fiber African diet with the high fat, high sugar US diet for two weeks. Prior to the beginning of the study, microbial composition heavily skewed toward Bacteroides (“good bacteria”) for individuals from Africa and Fermicutes (obesity-associated “bad bacteria”) for individuals from the US – consistent with the association of a prebiotic, high-fiber diet to promote the growth of healthy bacteria species. However, these ratios flipped after the dietary intervention; additionally the American volunteers developed a more diversified microbiome after two weeks on the African-style diet (another indicator of microbiome health), while the opposite occurred for the African volunteers on the American-style diet. Illustrating the connection between microbiome and metabolic health, a 2016 meta-analysis demonstrated that probiotic diets (i.e. foods such as yogurt, kimchi, sauerkraut, and kombucha which containing live strains of “good bacteria” that are able to colonize the gut) produce significant reductions in fasting plasma glucose in people with type 2 diabetes, sometimes even showing a corresponding reduction in A1c as well. It is important to bear in mind that the majority of probiotic studies have been short-duration and enroll only a small number of participants, but this study provides preliminary evidence that diets that promote a healthy microbiome can minimize the progression of type 2 diabetes and obesity – certainly encouraging news for CDEs hoping to counsel their patients about the importance of healthy eating.
• Ms. Jardine also emphasized the importance of exercise in maintaining a healthy microbiome, overviewing evidence that regular exercise improves the responsivity of the vagal nerve that mediates the communication between the gut microbiota and the brain. She further elaborated that the stress reduction aspect of exercise also plays a role in maintaining high levels of Bacteroides over obesity-associated Fermicutes.

Mode Matters: Matching Patient Goals with the Appropriate Exercise Regimen to Improve Diabetes Related Health Outcomes

Robert Powell, PhD (Marshall University, Huntington, WV)

Dr. Robert Powell delivered an energetic early-morning talk on the importance of exercise in diabetes education, challenging educators in the audience to emphasize specific and clearly-defined physical activity goals with the same rigor normally applied to nutritional or glycemic goals. To begin, he discussed the association between sedentary behavior and metabolic disease, positioning physical inactivity as one of the greatest health threats of our time. In short, “sitting is the new smoking.” Despite the widely-understood importance of exercise in diabetes prevention and management, Dr. Powell contended that people with diabetes receive a disproportionately low amount of support, education, and encouragement for physical activity as opposed to other aspects of diabetes care. To this end, his own research surveying various DSME programs revealed that markedly less instruction time is dedicated to exercise (17%) vs. nutrition (36%), medication (26%), and blood-glucose measurement (21%). Dr. Powell explained that people with diabetes are too often given vague recommendations about the importance of physical activity, without specific instructions on how exactly to structure their exercise and without any follow-up to hold them accountable to their goals. To this end, Dr. Powell rightly pointed out that educators would never rely solely on statements like “eat healthy” or “monitor your blood sugar” in explaining the complexities of nutrition and blood glucose monitoring, but “get more exercise” is often the only advice patients receive when it comes to physical activity. He shared his vision for the future of diabetes education, where the care and attention currently dedicated to reviewing meal plans and blood glucose numbers is also extended to defining the frequency, intensity, duration, and type (i.e. aerobic, resistance, or strength) of exercise that would most benefit each person with diabetes. We imagine that one reason for this lack of sufficient emphasis on physical activity is limited empirical data on the efficacy of specific exercise interventions, so we’d love to see more consensus among thought leaders and providers about best practices for exercise recommendations in diabetes prevention and management. Of course, the answer here is likely that physical activity needs to be personalized and tailored to the individual, but we still feel the diabetes field would benefit from clearer recommendations on this front.

Strategies to Get Action and Commitment from Your Toughest Patients

Debbie Hinnen (University of Colorado Health, Colorado Springs, CO) & Sam Thompson (Training and Coaching Consultant, Indianapolis, IN)

In this highly practical talk, Ms. Debbie Hinnen and Mr. Sam Thompson offered strategies to boost engagement in difficult-to-treat patients. Mr. Thompson likened healthy changes to New Year’s resolutions, noting that while 40% of Americans make a resolution at the beginning of the year, 80% abandon this by the end of February, some even sooner, leaving only 8% who report having achieved their resolutions. The parallel to diabetes care is clear: it takes hard work to behavior. To this end, Mr. Thompson and Ms. Hinnen outlined a five step framework for improving diabetes self-management: (i) Open with positivity; (ii) Share information; (iii) Identify actions; (iv) Explore barriers and motivation; and (v) Close with accountability. Opening with positivity involves setting the stage for success with a strong initial interaction with the patient; the HCP should focus on building rapport and identifying what features of a patient’s self-management are already good in order to establish a sense of momentum. Next, sharing information involves examining the patient’s current reality, educating them if there are gaps in their understanding, and establishing  focus on clear goals to prioritize. Here Ms. Hinnen was careful to point out that people learn in different ways, and HCPs should be attentive to whether their patients are “do-ers,” “watch-ers,” or “think-ers” in this context in order to best individualize care. For the next step,  identifying actions, Ms. Hinnen and Mr. Thompson, recommended limiting the number of goals to three or fewer, noting that if you set more than three goals, you won’t achieve any of them. The fourth step, is exploring barriers and motivation, involves  identifying present or potential future barriers to the patient’s success at achieving these goals, and creating a plan to minimize these. This involves gauging the patient’s level of confidence and exploring their underlying motivation for change. The final step is to have the patient review the plan and commitments, schedule next steps, and clarify any remaining concerns. We were so happy to hear from Ms. Hinnen, whom we have heard from at multiple AADEs, and we were not disappointed with her insights to improve care!

Food Insecurity and Diabetes Care

Lara Rondinelli-Hamilton (DuPage Medical Group, Plainfield, IL) & Jennifer Bucko Lamplough (Northern Illinois Food Bank, Batavia, IL)

This heartbreaking session explored the issue of diabetes care for individuals who suffer from food insecurity – the lack of consistent, dependable access to enough food for all household members for active, healthy living. Tragically, a whopping 13% of US households are food insecure, which translates to 15.8 million households and 42.2 million people. Food insecurity forces people to choose between paying for food vs. utilities, transportation, medicine, and housing and has a markedly adverse impact on health status by causing poorer dietary intake, more stress, competing demands, binge-fast cycles, and lack of stability. To this end, food insecurity increases the risk for cardiovascular disease and type 2 diabetes by 25%, increases the risk of kidney disease by 50%, and nearly doubles obesity risk. In addition to raising overall rates of chronic disease, food insecurity makes disease management incredibly challenging, and is associated with increased medication non-adherence, more food-medicine-medical supplies tradeoffs, poorer diabetes distress and diabetes self-efficacy, and increased diabetes hospitalizations and readmissions. Ms. Roninelli-Hamilton and Ms. Bucko emphasized that as frontline caregivers, CDEs can help by screening patients for food insecurity during their clinic visits and pointing them toward appropriate resources in the community. We so appreciated this session for drawing attention to an oft-overlooked issue in diabetes care and calling for greater action to improve these social determinants of health.

How Weight Bias Stands in the Way of Addressing Childhood Obesity

Theodore Kyle (ConscienHealth, Pittsburgh, PA)

Esteemed obesity expert Mr. Theodore Kyle (ConscienHealth, Pittsburgh, PA) discussed how unconscious biases interfere with efforts to reduce childhood obesity, both at the individual level (patient/provider interactions) and at the population level. According to Mr. Kyle, two kinds of bias are particularly prominent in the obesity arena: weight bias directed at people with obesity and intellectual bias favoring personal convictions about nutrition. Weight bias, the most pervasive of the two, flows from common negative assumptions about people with obesity. Mr. Kyle pointed out that even healthcare professionals are guilty of this; studies show that HCPs associate obesity with words like non-compliant, lazy, lacking self-control, weak-willed, sloppy, unsuccessful, unintelligent, and dishonest. Mr. Kyle argued that because of weight bias, too often the standard of care is no care in obesity; an astonishing 75% of primary care providers do not routinely address obesity, and if they do, they simply instruct the patient to lose weight without providing them with the tools or support to do so. Referral to intensive behavioral therapy is uncommon, and most physicians will not consider drug therapy, let alone metabolic surgery. Intellectual bias comes into play at a higher level, and refers to the troubling reality that policy decisions are too often based on myths and presumptions about nutrition and weight loss that aren’t proven. Mr. Kyle pointed to low fat dietary recommendations and labeling restaurant menus with calorie information as two examples of interventions that haven’t been proven to promote weight loss, despite their prominence in public policy. He closed with a call for greater scientific rigor and empathy in obesity care, underscoring that we all  have opportunities to acknowledge biases, build a stronger evidence base, conduct real experiments, think critically, and look for solutions that really work.

Current and Future Community Diabetes Self-Management Models

Linda Siminerio, PhD (University of Pittsburg, Pittsburg, PA), Athena Philis-Tsimikas, MD (Scripps Whittier Diabetes Institute, San Diego, CA)

Dr. Linda Siminerio (University of Pittsburg, Pittsburg, PA) began by introducing the PRISM study, which determined that Diabetes Self-Management Education (DSME) is effective in improving patient outcomes, with patients who received follow-up support from Diabetes Educators having the most psychosocial improvement. Educators were significantly better in support for empowerment and reducing distress for patients, with a statistically significant improvement in quality of life, and thus Dr. Siminerio recommends examining methods to promote this ability with other providers, and exploring opportunities for educators to support roles for peers and office staff. Educators were more likely to establish self-care goals and to follow self-care goals in SMS than other groups. Patients were most satisfied with educators, with the peer group next most satisfied. The study intervention trained primary care office staff, research staff, and peer participants on SMS interventions, delivered DSME to patients, implemented SMS interventions following DSME, compared outcomes and satisfaction between SMS interventions to determine the most effective SMS support mechanism, and assessed primary care office staff and peer participant satisfaction. The study took place at three community sites in Pennsylvania over a 6-month period. SMS follow up was conducted by peer SMS with monthly calls with phone scripts, by educator SMS with monthly calls, by PCP SMS with staff determining frequency of phone calls, and by usual care SMS with educator/PCP staff contacting the patient 2-3 months following DSME. 111 participants completed a 6-week study visit, 27 participants completed a 3- month study visit, and 12 participants were lost to follow up.

• The study groups were very representative of patients from rural, medically underserved areas, and the intervention was facilitated in a primary care setting. In addition to traditional diabetes clinical measures, the evaluation included behavioral, psychosocial, and process outcomes. However, the sample was uniformly white-Caucasian, and there was patient drop-out. The study had a short timeline and limited opportunities for recruitment, with interest and drop-out difficult to determine over the 6-month period. In addition, 50% of the peers were health professionals, which may not be translatable.

Exhibit Hall

Diabetes Technology

Abbott

Unsurprisingly, Abbott reps could not offer an update on the FDA review of the FreeStyle Libre consumer version, which was submitted nearly one year ago in 3Q16 – they likely did not have any information and of course could not have updated us if they did! That said, the company has its hands more than full with the US rollout of the professional (retrospective, blinded) version (FDA approved last fall), which reps said requires lots of coordination and education to get clinics up and running. We have been hearing incredible things about this product and believe that all patients should have access to “professional” or “intermittent” CGM, even if they cannot/do not want to wear a real time system. FreeStyle Libre Pro, branded alongside the empowering phrase “the more you can see, the more you can do,” was enough to cause significant bustle at the very expansive exhibit. Certainly this product will offer a lot more data for educators than intermittent fingersticks.

• After Abbott announced in July that it will release a next-gen Libre sensor with continuous, real-time communication (Bigfoot partnership), we speculated that FDA might actually be reviewing this next-gen version right now, which could help explain the lengthy real-time review, in addition to factory calibration. Although it could be possible, we also think it’s highly likely that the overworked Agency just needs extra time. We’d love to see the FDA gain more resources and be able to hire more people.

Ascensia

The Ascensia booth featured the Contour Next One BGM, showcasing it with the new slogan: “Remarkable accuracy in a whole new light.” We agree – the Diabetes Technology Society’s BGM Surveillance trial recently released results demonstrating that the Contour Next BGM (same strips as Contour Next One) was as the most accurate meter of the 18 tested. The booth – and signs on the conference escalators – highlighted the paired Contour Diabetes app, which syncs with the BGM via Bluetooth. We like the simple user interface, very easy-to-read numbers, and bright colors. The app is available for free download on the Apple and Google Play stores, though it has surprisingly low ratings of 2 and 2.5 stars, respectively. Dissatisfied reviewers cited issues with Bluetooth connectivity, editing entries, lack of customization, and general glitches. Ascensia is quite new to the digital health field – relative to competitors Roche and J&J – though we’re optimistic the company’s growing partnerships show serious commitment to innovation. The company has definitely stepped up digital efforts recently, including partnerships with Dexcom G5 Medicare, Insulet Omnipod Dash, Glooko, and Voluntis in the past few months – some real blue-chip deals!

BD

Like at ADA, BD had two separate booths at the AADE exhibit hall. Keeping in line with the most recent updates, a representative noted a projected 2018 launch for the type 2 patch pump and mentioned that progress for the Smart Sense pen cap is moving along; this was also slated for 2018, per the last update. The rep maintained that BD plans to keep the patch pump as simple as possible, adding “bells and whistles” only where needed – we think this is smart since the products of late that have done particularly well take away steps for patients rather than adding them. As for the MiniMed Pro-set, BD is still evaluating next steps with Medtronic. The reps said it is looking for new sites to expand the clinical trial to optimize user training materials. As a reminder, the 2Q17 update last week pegged a set re-launch in “FY18,” meaning October 2017-September 2018, which seems like an appropriately wide window. Representatives seemed excited about the Medtronic partnership, noting that the timing of the broader MiniMed 670G rollout coordinates well with the MiniMed Pro-set re-launch if all goes well. Meanwhile, a very cool unbranded “2.0 Lab” asked educators to vote on needs in the type 2 community, which BD plans to incorporate into some kind of campaign. At the top of the list was a patient lifestyle app (it was not exactly clear what that means – presumably a useful app associated with food, exercise, etc.), followed closely by flexible dosing and reduced number of injections; at the very bottom were dose capture reports and having a large pump reservoir of insulin. We stopped by fairly early in the day, so the results streamed in real-time at the booth may have since changed – it was surprising to see dose capture so low, but perhaps that reflects that a minority of patients are on insulin and that educators may not be the ones titrating insulin. We certainly believe more would benefit from greater education and help on optimal doses of insulin.

Companion Medical

Companion Medical CEO Mr. Sean Saint reaffirmed that the Bluetooth-enabled InPen will still launch sometime in 2017. Despite the pre-market status, another rep told us that CTO Mr. Michael Messinger, hired in May after leading Dexcom’s app and cloud software teams, will be designing some upgraded features of the application. We can’t wait to see what Mr. Messinger comes up with …

DarioHealth

The DarioHealth booth showcased its all-in-one headphone jack BGM. The representative noted the recent approval of the Dario app for Android, which should hit the Google Play store in two to three weeks. It’s taken a surprisingly long time for DarioHeath to obtain Android clearance, but now that it’s been achieved, DarioHealth has plans to ramp up social media marketing efforts. DarioHealth recently partnered with Byram Healthcare, a one-stop-shop for diabetes products, which by their estimate in the press release will increase their coverage to 30% of US consumers with diabetes. Since expanding third party insurance coverage for US consumers in June, DarioHealth has also obtained some reimbursement through Aetna, United HealthCare, and various Blue Cross Blue Shield programs. Consumers interested in reimbursement can fill out a form located on the DarioHealth website to assess their coverage. We have yet to hear updates on DarioHealth’s long-term AI guidance goals, as well as future aims to explore the diabetes prevention landscape and incorporate other biomolecular tests, such as cholesterol, into its platform.

Dexcom

Dexcom’s booth at the front of the hall was smaller than at ADA, but attracted a steady stream of educators with bright white styling and ample TV screens. Reps showed off the updated version of Clarity (now with AGP reports!); shared flyers advertising Medicare coverage of G5 (first shipments started as of last week’s 2Q17 call, though Dexcom needs to confirm the claims actually go through); highlighted Android G5 (launched at ADA); and emphasized Dexcom’s “CGM first” message with bold signage at the top of the booth and handouts on the growing number of CGM in MDI studies (DiaMonD, GOLD, COMISAIR). Reps were also showing the touchscreen receiver to attendees and coming this fall – see our take on it from ADA. We learned that the Medicare bundle is actually not shipping the G5 touchscreen receiver yet, but using the current G5 receiver. This was our mistake for implying this in previous Closer Look coverage. A prominent sign at the front of the booth advertised book signings with our own Adam Brown for Bright Spots & Landmines: The Diabetes Guide I Wish Someone Had Handed Me. As we understand it, the hundreds of books in Dexcom’s booth went pretty quickly! Truly, it is wonderful to see the transformative products at the booth and it is very clear that the standard of care is changing for people with diabetes. We were glad to see a very steady stream of educators into Dexcom’s booth, indicating more familiarity and interest in CGM.

DiabNext

DiabNext had a number of updates on its “all-in-one” digital diabetes management platform, which includes a cable to Bluetooth-enable non-connected meters (think Glooko’s MeterSync Cable), an insulin pen clip attachment to capture doses (slightly dubious in design), an app that uses AI and pictures to calculate carbs on the plate, and a connected pill bottle top. The company will launch 10,000 sets – including the smart pen attachment, connected pill bottle top, and BGM cable – across the world in October for a trial that will begin this year and proceed into 2018. We saw a rather impressive demo of the snapcarbs app (AI carbohydrate evaluator, based on picture of food), which will reportedly launch in September. It estimated that an Asian noodle salad had 83 grams of carbs, which seemed reasonable (although no way to verify, since the salad did not have a label on it). Finally, the company is in talks with the governments of Singapore, France, Japan, and Taiwan to begin pilots with the goal of achieving reimbursement. We like the all-in-one approach and the software looks encouraging, though the initial smart pen and BGM hardware is pretty clunky and doesn’t instill confidence right off the bat – still, there is no question this is a service that is needed and the upcoming trials should be illuminating.

The diaTribe Foundation

The diaTribe Foundation hosted its first-ever booth at this year’s AADE meeting, getting 300 copies of our own Adam Brown’s diabetes guide, Bright Spots and Landmines, into the hands of diabetes educators from across the country in less than one hour – wow! We need a bigger budget for our books next time! The demand kept coming and The diaTribe Foundation will be shipping hundreds more additional free copies of in the coming weeks from educators who requested them right up until the exhibit hall closed! Over the weekend, HCPs and patients offered encouraging feedback: One person who has lived with type 1 diabetes for >55 years shared that the book has changed how she approaches her disease. Another educator shared that she’s going to get this helpful book to all of her patients. A number of other booth visitors praised diaTribe.org as a valuable resource for real-world patients and providers. The diaTribe Foundation extends immense thanks to AADE for its generous support in making this possible, as well as to Dexcom and Arkray for getting Bright Spots & Landmines into the hands of 400 and 100 more providers, respectively. In turn, thank you to AADE and so many educators for helping us get the word out about diaTribe and Adam’s book, Bright Spots and Landmines. This now has over 100 five-star reviews on Amazon – can you help us get to 200?

Fit4D

Fit4D delivers personalized, one-on-one coaching to in-need populations entirely over phone, text, email, online events, and online content. The company’s goal is to extend the reach of educators using technology, and it partnered with Glooko in April to adding CDE coaching to Glooko’s data management platform and Population Tracker. The booth representative emphasized that all coaches are certified diabetes educators, and that the program has driven lower A1c’s and improved medication adherence. She also mentioned that a peer-reviewed study demonstrating these outcomes is in the works for publication next year. We were particularly glad to hear that the program is reimbursable through health plans and is covered by both Medicare and Medicaid. CDEs are responsible for logging patient data through the Fit4D online platform, which includes coaching content and analytics. We were appreciated hearing from CEO and founder of Fit4D, Mr. David Weingard, as part of a panel of key industry thought leaders on the last day of AADE. Keep your eye out for our coverage of the session coming your way soon!

Glooko

Glooko showed off its fancy new touchscreen, NFC- and Ethernet-enabled transmitter, which is currently piloting in Sweden and expected to launch later this year. As shown in the photo, this is a step up from the more utilitarian Diasend Transmitter previously offered to health systems and clinics. Said the company rep, “Instead of having to interpret beeps, this tells you what the Transmitter is doing in plain language.” Nice to see a more provider-friendly system fall into place as the Glooko/Diasend merger progresses!

Insulet

Insulet’s big booth drew educators into the center with video demonstrations of Omnipod Dash. Unlike the ADA booth, the Android-based, Bluetooth-enabled Dash PDM was not on display, presumably because it would be pre-marketing. (FDA submission expected in 4Q17.) This time, attendees could watch a video of Dash and were asked to take a survey about the ease of training patients on the system – very smart of Insulet to continue using booths to collect market research! (It also gave a Dash survey at ADA.) The very smart “demo pod” program continues, this time donating $5 to AADE for every demo pod worn – educators seemed to love this and we certainly did too! On the periphery of the booth, Insulet-provided Glooko was on display, a sign of continued commitment and enthusiasm for this valuable data partnership. “Podders” living life with Omnipod were impossible to miss throughout the booth, while signs on the top highlighted the innovation roadmap leveraging Dash (Horizon Automated Glucose Control, U200, U500). Continuing Insulet’s focus on MDI – and away from tubed pump competition – this slogan was what we noticed leaving the booth: “Hello, Independence. Goodbye, Multiple Daily Injections. The control of a pump. The comfort and convenience of the Pod.” This is great marketing as we believe it will move right into the greatness of automated insulin delivery as the company moves in that direction.

iSage Rx

Amalgam Rx made its exhibit hall debut by showcasing iSage Rx, the prescription-only basal titration app. According to CEO Mr. Ryan Sysko, the reps had been getting very positive reception and by the time we stopped by the sky-blue booth on day two, over 30 attendees had already registered to have a representative reach out to them to discuss set up in their practices. By the end of the conference, the company shared that more than 100 educators viewed a demo of the provider portal and patient application and requested access to start using iSage. He also told us that a couple of big health centers have signed on, adding to the feeling that the insulin titration software is getting some early traction. Assuming the clinics don’t already have a titration system, it was logical to try iSage Rx, considering the company is offering it for free for a limited time. On the pipeline, management now aspires to achieve FDA 510(k) clearance of the basal+GLP-1 titration engine by the end of the year – it was previously expected by the end of June. Things always take longer… It was great to see iSage Rx join the growing class of dose titration products in the exhibit hall – see our piece from May announcing the company’s launch for a deeper dive.  

J&J (OneTouch)

The representatives at the OneTouch booth were particularly excited about the OneTouch Reveal mobile app (Apple Store, Google Play), which syncs with the OneTouch Verio Flex BGM. The app separates data out by meal and blood glucose range, using colors and shapes to easily identify trends. We particularly liked the feature which highlights trends for the user, literally connecting the dots between data points. The report can be texted or emailed as a pdf, and can also be exported to Excel. Users can add clinic information to facilitate direct data flow and are able to sync the app with Apple Health. The representative referenced some physicians who have mentioned that their older patients uncomfortable with the technology prefer not to use the app – no problem, data points can still be uploaded right in the provider’s office as before. We were surprised not to hear any updates on the OneTouch Via bolus-only insulin delivery patch, though signs along the side of the booth advertised it with an “FDA clearance just received” sticker. The device was unveiled for the first time at ADA, though there was no update on the 2Q17 call. The product’s updated manufacturing process (submitted in November) received FDA 510(k) clearance in June. Said the rep at ADA: “We are focused on ensuring a perfect launch for patients … Our goal is that no patient will start on Via and not continue.” Wow, we love hearing this! We have long been optimistic about this technology and are looking so forward to seeing it launched. We certainly hope J&J moves forward on this front, even though it is considering a sale of the Diabetes Care franchise (LifeScan, Animas, Calibra). This is one of the most promising new technologies around – we think it would work particularly well for those on LifeScan’s glucose monitoring devices, of course, but also for those on Libre, who would have a very good sense of when to press for more insulin.

Medtronic

Medtronic’s MASSIVE booth was dotted with table stations, iPads, and the latest products throughout, including the MiniMed 670G hybrid closed loop, MiniMed 630G, and Professional CGM with iPro2 and the myLog app (with partner Fitbit). The standalone Guardian Connect CGM was not on display, meaning the FDA review has now stretched well past one year. A slogan above the main desk, “Always by your side” seemed fitting for the educator audience and relevant to the 670G. Customer photos were also plastered on the edges of the booth, further highlighting patients on the MiniMed 670G while playing soccer, etc. We had a chance to see the Guardian Sensor 3 up close using a “developer edition” of the Microsoft HoloLens device – the “mixed reality” approach was pretty interesting, projecting a holographic image of a person with diabetes and showing the sensor up close. Though the HoloLens didn’t knock our socks off, a rep noted the cool potential for new diabetes education and training possibilities with the device – e.g., more interactive MiniMed 670G HCP training. We like seeing experiments like this and are glad to see Medtronic investing in next-gen platforms. Though the tech community often vacillates between “AR/VR is going to change the world” and “AR/VR is overhyped,” we see definite potential for more immersive patient and HCP education, interesting approaches to exercise, and beyond.

• Upon looking at the Medtronic website, we noticed a Priority Access Program FAQ, which again suggests the 670G launch is still proceeding very cautiously (in line with Keystone commentary). Interestingly, the FAQ page says MiniMed 670G pump and transmitters will be shipped first, followed by a separate Guardian Sensor 3 package between 30-90 days after the pump shipment. The page says this is to verify insurance coverage for sensors, and we’ve since confirmed this also relates to the sensor shortage, high worldwide demand for Medtronic CGM, and manufacturing scale-up. In other questions on the FAQ page, Medtronic cites delays due to HCP training (“We’re getting to healthcare provider practices as quickly as we can, but it is taking time”) and learning from the customer training phase. The FAQ page does note that non-Priority Access Program shipments will begin in late summer/early fall, which feels slightly ambitious – as of Keystone a few weeks ago, almost none of the 20,000+ Priority Access members had received their systems yet.
• To get a further $299 credit, Priority Access Program participants can opt to give Medtronic some valuable data: upload a patient story (2-4 minutes or ~500 written words), complete three surveys (20-40 minutes each), and do at least one CareLink upload. This is pretty smart of Medtronic, and the credits are given for each activity (those who complete all activities will get a total of $299 in account credit). 

mySugr

The mySugr “Make diabetes suck less” booth was hopping, and everyone was smiling as they congratulated the company reps on the recent Roche acquisition (late June). Management was uniformly relieved that the negotiations have ended and glad that nothing else has really changed – business as usual, only as part of the Roche family. We did not notice any Roche branding in the booth – great to see the standalone stipulation is holding true. We’ll be fascinated to see how mySugr expands with additional resources from Roche, particularly to delve deeper into the near limitless data it has captured from its >1 million registered users. We also heard that progress in Germany, where payer VKB is launching a mySugr hassle-free package for insulin treated patients at €999 per year, is “going well,” though no data were shared – this includes coaching, a BGM with unlimited strips, and population management. The company is pushing forward on talks with multiple other payers worldwide. We can’t wait to see how uptake and reimbursement for one of the more successful digital health products develops in the next year or two. We also wonder what plans there are for pattern recognition and other uses of CGM data in mySugr. The app can import data from Dexcom’s G5 (via Apple Health) and Abbott’s FreeStyle Libre (direct backend connection), and a Medtronic CareLink backend connection agreement has been signed (announced in November). CGM data is intentionally not included in the app’s statistics (the company wants it to be separate from fingerstick data), though we see lots of potential here, especially with mySugr’s well-received bolus calculator, ability to take meal pictures, logging insulin doses, and search functionality…

One Drop

Though not discussed in the booth, the most notable news to come out of the One Drop camp is that it, together with Mannkind, will launch the A-ONE RCT to study the effect of integrating Afrezza inhaled insulin and the One Drop digital diabetes care platform. A drug-device combo – nice! As we understand it, this trial is the first step of the companies’ collaboration, first announced back in May. In the study, 400 people with type 2 (who are not currently enrolled in a diabetes education/coaching program and have never taken Afrezza) will be randomized to either Afrezza+One Drop Premium or One Drop Premium alone. Now that is a cool design and there is clear upside here for One Drop. (MannKind risks no incremental benefit over One Drop alone, so this is more of a gamble for them.) As a reminder, the Premium offering entails unlimited strips and 24/7 in-app support from CDEs. One Drop’s VP of Health & Behavioral Informatics Dr. Chandra Osborn said the trial will start upon receipt of IRB approval, expected sometime in September. Outcomes metrics will include changes in A1c, quality of life, self-care, and treatment satisfaction. We would bet that real-time coaching + mobile education will absolutely improve the use of Afrezza, but the question is, will it be better than use of One Drop alone – particularly when the primary endpoint is A1c? We hope the answer is yes – many who use Afrezza swear by it, noting the blunted postprandial highs and fewer lows than injectables. We would love to see professional CGM leveraged in the study, to ensure these post-meal excursions (highs and lows) are captured. For One Drop, positive data would add to a growing body of literature consisting of nine peer-reviewed outcomes shared at medical meetings (see two from ADA 2017 here and here) and a paper in press at JMIR Diabetes (“Using the One Drop Mobile app is associated with reduced A1c”). Assuming the results indicate Afrezza+One Drop Premium is more effective than One Drop Premium alone, would the two companies commercialize a bundled product to entice payers? We’d love to see more combination approaches.

• A One Drop rep told us that the app now has ~350,000 registered users, up remarkably from ~200,000 registered app users in May. Through arrangements with industry and payers (including a deal with large UAE insurer Daman Health), One Drop expects to boost user base significantly. The One Drop model seems to be quite scalable – the rep told us that there are a significant number of coaches on staff, and each can tend to thousands (!) of clients at a time. That’s what automation does …

Roche

Roche returned to the exhibit hall following a notable absence at ADA. The company’s real estate focused on the Accu-Chek Guide BGM, launched in the US in May, and the accompanying SimplePay Savings Program, which grants a free meter and strips for $0.22-$0.40 each without insurance. We love it! Reps were especially eager to tell us about the extremely reasonable pricing, as well as the Accu-Chek Delivers Program, which offers enhanced physician support. This was great to hear. In a cheeky competitive display to call attention to the Guide test strip’s wide application area (something we noted in our test drive), the booth also featured a Price is Right-style wheel. Instead of numbers, the wheel had life size strips from Roche and various competitors, and instead of the arrow that indicates which number was selected by a spin, there was a Guide strip. HAHA! The goal is to align the Guide strip on the wheel with the stationary one. We did so on our very first spin, and won our very own set of Accu-Chek-labeled measuring spoons. Next stop, Price is Right!

Tandem

Tandem’s inviting, open-aired, modern booth drew attendees at the front of the hall to learn the latest about t:slim X2. Screens along the edge of the booth drew us in, and we finally snapped a picture of the planned t:slim X2 mobile app for displaying key pump data, uploading data to t:connect (“Never upload a pump again!” – awesome!), and integrating with CGM – it looks very user friendly (see picture below). As of Tandem’s ADA Media Day, a launch of this app is possible this year. The screen showed the CGM trend graph, recent boluses and basal rate, insulin on board, pump reservoir and battery, and even time-in-range right on the home screen! Incredible. The scrolling slides also emphasized the updated pipeline timing from the 2Q17 call: (i) t:slim X2 with G5 is still under FDA review (no launch timing shared, but we’d speculate it’ll be some time this year); (ii) launch of the predictive low glucose suspend device in “summer 2018” (delayed ~1 quarter from the previous “early 2018”); and (iii) launch of the TypeZero treat-to-range system by the end of 2018. We saw several attendees with diabetes happily wearing the t:slim pump around the hall.

Valeritas

The Valeritas booth showcased the V-Go basal and bolus insulin delivery device indicated for 24-hour wear. Educators visiting the booth were particularly interested in the usability, wearability, and accessibility of the device. Not surprisingly, the representatives had positive responses for all three categories, and referenced studies on the Valeritas website, which indicate that nine out of ten patients who try the V-Go stay on the device. We have heard incredibly positive things from patients on the device but also some wishful thinking from those who can’t yet get access. We weren’t able to find this particular “9 out of 10” data, but the website does provide a comprehensive assortment of publications and posters with convincing evidence of V-Go’s benefits. Our sense is that patients do very much like V-Go once they get on it, but that awareness and reimbursement have challenged the company. Luckily, Valeritas has $51 million in cash as of 1Q17, meaning more than a year of runway to scale the business and invest in sales/marketing.

Voluntis

News from Voluntis was that everything is proceeding smoothly: Pilots around the US with partners are moving forward, an integration with Livongo and another with Ascenia are in development (no launch time confirmed), and as announced last month, the company recently received FDA clearance and a CE mark for the titration of Toujeo. Lantus and Levemir are already supported, and all basal insulins and GLP-1/basal insulin combos are in the works. Insulia (the name of the app) will launch shortly on the EU market. We continue to wonder when this product will really truly launch, since it was a first-in-class FDA clearance last year – we’d love to see patients taking advantage now!

WellDoc

The WellDoc booth – the first standalone booth for the company at a major conference after occupying territory in other company’s booths in the past – greeted visitors with an oversized phone, presumably a Samsung phone, suggesting that the BlueStar C/Samsung Health integration may be coming soon. Similarly, reps indicated that the J&J integration is “moving along” – as of the J&J 2Q17 update, patients can now sync OneTouch Verio Flex BGM data to WellDoc’s BlueStar software. We’re not sure if this also means that the companies are co-marketing the integrated product, or if that is forthcoming. Reps were most excited about the “Diabetes Digital Health Learning Network,” to support educators in their quest to leverage digital health in their clinical care, which launched in collaboration with AADE on Friday. Within the Learning Network, led by past AADE President and current WellDoc Vice President of Clinical Advocacy, the beloved Ms. Malinda Peeples, self-identified that AADE members will strive to develop best practices for incorporating technology-enabled solutions for DSMES. The stated objective is to “define the leadership role for diabetes educators in population health and to leverage patient-generated health data to improve outcomes.” Nice! This trailblazing initiative seems like an effort to build the category of prescribed digital health apps, and might smooth the transition for educators who are daunted by technology. Applicants for the group are currently being sought – if you are an educator with a type 2 practice, you can apply here. The AADE-WellDoc formal collaboration began in January, when the two announced the integration of AADE7 Self-Care Behaviors into BlueStar.

Diabetes Therapy

AstraZeneca

AZ’s exhibit hall booth featured three diabetes products: SGLT-2 inhibitor Farxiga (dapagliflozin), fixed-dose combination Xigduo (dapagliflozin/metformin), and GLP-1 agonist Bydureon (exenatide once-weekly). The compact display included interactive touch screens where attendees could explore each therapy through patient case studies. The emphasis on Farxiga and Xigduo was expected, as AZ management has clearly established the SGLT-2 inhibitor business as its leading diabetes priority and as a major company priority overall. We were glad to note substantial promotion around Bydureon as well – every sales rep was wearing a sample Bydureon pen around his/her neck to demo for booth visitors. The Bydureon pen is currently the more patient-friendly mode of delivery of the agent (as opposed to a single-dose reconstitution kit), but still requires an elaborate and time-consuming “mixing” process before injection. AZ has submitted a new Bydureon autoinjector to the FDA, and is expecting a regulatory decision in the second half of 2017. In our view, this autoinjector will offer a much more patient-friendly mode of exenatide delivery, which could serve as a needed boost to the Bydureon business (sales were down 6% YOY in 2Q17, to $146 million). We asked an AZ rep about timing for Qtern’s US launch, but no update was available. This fixed-dose combination of dapagliflozin/saxagliptin (AZ’s DPP-4 inhibitor Onglyza) was FDA-approved in February 2017 and we can’t wait to see this on the market.

Blink Health

Blink Health occupied a small but eye-catching table at the periphery of the exhibit hall. Adorned in a flashy red and white color scheme, the table was framed by large banners proclaiming “Tell your patients! Blink Health is giving away metformin, glipizide, and pioglitazone for free, for a year.” The tablespace was stacked with pamphlets describing the details of Blink Health’s patient assistance program, and representatives were on hand to provide further explanation. Any effort to expand patient access to drugs is greatly appreciated, though it’s important to point out that these three medications are already generic and fairly inexpensive to begin with, plus we do not even think glipizide should be on the market due to all the association with hypoglycemia, weight gain, and congestive heart failure. We found it quite curious that Blink Health’s booth made no mention of its partnership with Lilly to offer discounts on Humalog, Humulin, and Basaglar to patients facing high out-of-pocket costs – as we understand it, even after Blink Health terminated its deal with Express Scripts, Lilly’s insulins were still going to be made available at steep discounts on Blink Health’s platform.

J&J (Janssen)

SGLT-2 inhibitor Invokana occupied a mere sliver of this large exhibit (with most of the booth dedicated to One Touch and the device side of J&J’s diabetes business). An unassuming stand listed three products in the canagliflozin family: (i) standalone Invokana (canagliflozin), (ii) fixed-dose combination Invokamet (canagliflozin/metformin) with twice-daily dosing, and (iii) once-daily Invokamet XR (canagliflozin/metformin extended-release). One monitor displayed safety considerations for HCPs prescribing Invokana, while another reminded attendees that Invokamet can be used as first-line therapy in type 2 diabetes (the FDA approved this first-line indication for the fixed-dose oral combination in May 2016). This latter screen, in bright blue, positioned Invokana and Invokamet as viable, reasonable choices for recently-diagnosed patients, especially if they’re starting with a high baseline A1c. Indeed, we’d love to see SGLT-2 inhibitors used earlier in the course of disease (when safe and well-tolerated by the patient) to more efficiently target glycemic control and weight loss. There was not much information about reduced CV events since that is not “indicated” yet though it is published!

Lilly

Lilly’s large, central booth drew quite a crowd with one of the most popular espresso stations in the exhibit hall. Free-standing wall displays radiated outward from the center, outlining information on the company’s various diabetes products. Displays for GLP-1 agonist Trulicity (dulaglutide) and BI-partnered SGLT-2 inhibitor Jardiance (empagliflozin) were given prime location at the front corners of the booth. Promotional materials for Jardiance’s new CV death indication were out in full force, featuring slogans such as “CV death has a new opponent” and imagery of a heart superimposed with the words “only Jardiance.” Behind these displays, smaller sections featured DPP-4 inhibitor Tradjenta (linagliptin), fixed-dose combination Glyxambi (empagliflozin/linagliptin), basal insulin Basaglar (biosimilar insulin glargine), the Humulin U500 KwikPen, and the Humalog (insulin lispro) U200 KwikPen. This was quite similar to Lilly’s displays at ENDO 2017 and AACE 2017, and we were pleased to see a reappearance of the section on patient affordability and access (tagline: “Helping more patients get the medicine they need”). We admire Lilly’s commitment to lowering patient out-of-pocket costs, including its direct discount program with Blink Health (though Express Scripts has since dropped out of this agreement) and its ongoing negotiations with payers to create a separate, copay-free benefit category for insulin.

• Though not reflected in Lilly’s booth, we learned that the company recently expanded its collaboration with Disney to launch T1 Everyday Magic on Instagram. The handle @t1everydaymagic builds on the existing online resources at the T1 Everyday Magic website to provide families with information, advice, and social support surrounding issues in type 1 diabetes. This initiative further illustrates the company’s commitment to improving the lives of patients with diabetes. We’re always glad to see pharma companies recognize that patients will do best on their products if given adequate support tools, whether this be insulin titration software, other digital health apps, or a platform that facilitates easy participation in the diabetes online community. We still remember when Lilly Diabetes head Mr. Enrique Conterno himself introduced this idea to the diabetes community.

MannKind

MannKind’s booth in the exhibit hall was larger than we’ve seen at other diabetes conferences over the past couple years, featuring plush purple carpet and an eye-catching slogan: “Mealtime moments can be unexpected.” One poster showed a close-up of the Afrezza inhalation device in someone’s hand – it was small and unintimidating, balanced on just a couple fingers, looking nothing like the clunky inhalation device for Pfizer’s now-discontinued Exubera. MannKind reps walked booth visitors through PK/PD graphs on the wall, explaining how Afrezza insulin is absorbed in ~12-15 minutes, while it takes ~three hours to return to pre-meal blood insulin levels. The company’s exhibit hall presence fit well with its leading commercial strategy around Afrezza, in that most emphasis was on the faster-acting nature of this prandial insulin product as opposed to the inhaled aspect. We think this approach to marketing and education is wise, as it distances Afrezza from Exubera and draws attention to the distinct advantages of faster onset/faster offset – namely, reduced hypoglycemia risk. It’s absolutely true that mealtime moments can be unexpected (people don’t know exactly when their food is going to arrive at a restaurant, for example), and what’s currently available for bolus insulin is simply not good enough. Afrezza could help fill this unmet need in diabetes therapy, provided MannKind’s commercial strategy continues to gain traction and sales of the inhaled insulin pick up in the coming months. We note that patient feedback on Afrezza has been quite positive, and that MannKind has filed with the FDA for an ultra-rapid-acting label claim. If this designation is approved (a decision is expected by September 30), the company could further ramp up its marketing around Afrezza’s faster-acting nature, which we believe would meaningfully boost uptake.

• Though not mentioned in the booth, MannKind and One Drop just announced plans to launch the A-ONE RCT, investigating the effect of integrating Afrezza and the One Drop digital diabetes care platform. A drug-device combo – nice! The announcement notes that this trial is the first step of the companies’ collaboration, first announced back in May. In the study, 400 people with type 2 (who are not currently enrolled in a diabetes education/coaching program and who have never taken Afrezza) will be randomized to either Afrezza+One Drop Premium or One Drop Premium alone. Now that is a cool design and there is clear upside here for One Drop. (MannKind risks no incremental benefit over One Drop alone, so this is more of a gamble for them.) As a reminder, the Premium offering entails unlimited strips and 24/7 in-app support from CDEs. One Drop’s VP of Health & Behavioral Informatics Dr. Chandra Osborn said the trial will start upon receipt of IRB approval, expected sometime in September. Outcomes metrics will include changes in A1c, quality of life, self-care, and treatment satisfaction. We would bet that real-time coaching + mobile education will absolutely improve the use of Afrezza, but the question is, will it be better than use of One Drop alone – particularly when the primary endpoint is A1c? We hope the answer is yes – many who use Afrezza swear by it, noting the blunted postprandial highs and fewer lows than injectables. We would love to see professional CGM leveraged in the study, to ensure these post-meal excursions (highs and lows) are captured. For One Drop, positive data would add to a growing body of literature consisting of nine peer-reviewed outcomes shared at medical meetings (see two from ADA 2017 here and here) and a paper in press at JMIR Diabetes (“Using the One Drop Mobile app is associated with reduced A1c”). Assuming the results indicate Afrezza+One Drop Premium is more effective than One Drop Premium alone, would the two companies commercialize a bundled product to entice payers?

Merck

Merck’s AADE booth was off to one side in the exhibit hall this year, but still drew quite a substantial crowd with its mainstay frozen yogurt stand and a customized station where conference attendees could design and print their own scientific posters. Most of the booth’s medical real estate was devoted to DPP-4 inhibitor Januvia (sitagliptin) and fixed-dose combo product Janumet (sitagliptin/metformin). Attendees could read patient stories about Januvia and Janumet on interactive, touch-screen panels. Approximately one-fifth of the booth focused on the company’s vaccine Pneumovax 23 (pneumococcal vaccine polyvalent). Despite fluctuating DPP-4 inhibitor sales of-late, Merck’s Januvia franchise still captured 61% of the $2.5 billion market in 2Q17 – read our most recent Merck earnings report for more on the company’s diabetes business. We look very forward to FDA approval of the combo DPP-4 inhibitor/SGLT-2 inhibitor from Pfizer!

Novo Nordisk

Victoza (liraglutide) was the star of Novo Nordisk’s bustling corner booth, which featured a large image of the sleek, light blue GLP-1 agonist pen as a backdrop on its center wall. Adorned with light wood paneled desks and crisp white chairs in the company’s signature minimalist aesthetic, the booth’s signage was split equally between Victoza and next-generation basal insulin Tresiba (insulin degludec), with a standalone panel dedicated to each. Victoza materials highlighted the drug’s “3-for-1 benefits” – A1c efficacy, weight loss, and low rate of minor hypoglycemia – and emphasized that it is the #1 prescribed GLP-1 agonist globally (perhaps a nod to increasing competition in the GLP-1 agonist market). Tresiba materials featured a skydiving/parachute motif with the slogan “a proven A1c descent.” Data featured in the booth focused especially on Tresiba’s flexible dosing indication and the fact that it is the only basal insulin pen with a maximum injection dose up to 160 units – this latter point is clearly part of Novo Nordisk’s efforts to position Tresiba for patients with type 2 diabetes and higher insulin requirements. The fixed-ratio combination product Xultophy (insulin degludec/liraglutide) was represented in name only on the inner lining of the booth’s overhead banner, which was depressing overall given the incredibly positive KOL feedback on this compound. Novo Nordisk management has emphasized in the company’s recent earnings updates that Tresiba and Victoza remain greater commercial priorities than their combination for now, which is quite depressing given the results. The Tresiba and Victoza franchises are individually major drivers of growth for Novo Nordisk, and reps at Diabetes UK 2017 explained the company’s strategy as an effort to cultivate familiarity with these two relatively new-to-market drugs before emphasizing the combination. We did not buy this given that Victoza was approved in 2010! We were surprised not to see any mention of the obesity medication Saxenda (liraglutide 3.0 mg), which was featured in a dedicated booth of its own at ADA, AACE, and ENDO. We interpret this as a reflection of the AADE agenda’s primary focus on diabetes rather than any sign of diminished enthusiasm for the obesity product on Novo Nordisk’s part.

Sanofi

The perimeter of Sanofi’s exhibit was lined with messaging around fixed-ratio combo product Soliqua (insulin glargine/lixisenatide), just launched in early January. Reps highlighted that the medicine comes in a pre-filled pen from the SoloStar family, a familiar device for patients who were already on Lantus (basal insulin glargine). Notably, Sanofi is positioning Soliqua as a basal insulin intensification option in the US due to its FDA-approved indication only for patients not at goal on basal insulin or lixisenatide monotherapy – since commercial uptake of standalone lixisenatide (branded as Adlyxin in the US) has been low, we imagine a majority of people starting Soliqua were taking Lantus previously, so the familiar face of a SoloStar pen could be quite encouraging and patient-friendly. Sanofi reps working the exhibit also underscored the benefit of one injection instead of two, as well as one co-pay instead of two. Both features make Soliqua a more convenient treatment option for real-world patients. While the company is not “touting” Soliqua as a weight loss therapy, reps emphasized that the drug does indeed offer a benefit to body weight (clinical studies showed a treatment difference of ~3 lbs for Soliqua vs. Lantus). Walking further into Sanofi’s booth, visitors could read about Toujeo’s flat PK/PD profile over 36 hours (on a very large poster, right behind the smoothie station!). A smaller monitor displayed safety/efficacy data for Lantus on one side, and for rapid-acting insulin Apidra on the other. This latter screen described Apidra as the only rapid-acting insulin product with a $0 co-pay option for commercially-insured patients, and also captured how the agent (insulin glulisine) shows efficacy across a range of BMIs. Lastly, we spent some time immersed in a virtual reality simulation of hypoglycemia at Sanofi’s booth. With black goggles and headphones on, we heard the sobering story of one Sanofi employee who experienced a severe hypoglycemia episode on an airplane. We were glad to see this explicit attention not just on hypoglycemia, but on the patient’s real-world experience with hypoglycemia. Advanced therapies (like Soliqua) that could reduce hypoglycemia risk are so important, and we hope to see continued efforts to increase patients access to these newer, safer products.

 

-- by Adam Brown, Ann Carracher, Abigail Dove, Brian Levine, Payal Marathe, Maeve Serino, Emily Yang, and Kelly Close