In this fourth installment of AADE 2017 highlights, you’ll find coverage of Chris Bergstrom’s keynote speech on all-things digital health and a trifecta of beyond-A1c talks from our own Adam Brown, JDRF’s Dr. Aaron Kowalski, and Dr. David Marrero (Univ of Arizona). In the exhibit hall, we heard notable updates from One Drop, Medtronic, Glooko, and saw a strong digital health presence (including a veritable insulin dose titration invasion!). Plus, The diaTribe Foundation hosted its first ever booth in the name of distributing Adam’s new book, Bright Spots & Landmines to attending educators for free!
Our therapy highlights include not one, but two Sanofi-sponsored dinner symposia – one discussing fixed-ratio combo product Soliqua (insulin glargine/lixisenatide) and how to pitch it to patients (this isn’t the problem and we don’t think this will be challenging), the other on optimizing basal insulin therapy (featuring Dr. Nathan Painter, Ms. Teresa Pearson, and Dr. Guillermo Umpierrez) – plus a fascinating exploration of the similarities and differences between various agents in the GLP-1 agonist class. Day #4 also featured the talk that many educators Tweeted about as “the best session of AADE17” – Dr. Robert Gabbay’s perspective on value-based healthcare and how diabetes education will play a critical role. Read on for our coverage of this brilliant talk and many others, plus our pickups from the 29 exhibits we perused …
If you missed our previous installments of AADE highlights, you’ll find day #1 here (Dr. Susan Cornell Pharmacology Booth Camp and CDC’s Dr. Ann Albright on DPP), day #2 here (CANVAS commentary galore; Dr. Bode on insulin titration), and day #3 here (OpenAPS’s Ms. Dana Lewis talks DIY updates; Adam Brown on tech in the wild.
Diabetes Technology Highlights
1. In a whirlwind keynote entitled “Let’s Get Digital,” BCG’s Mr. Chris Bergstrom (with help from videos of well-known educators and one CEO), instilled confidence that we are at the cusp of a big transition in the way diabetes is managed, thanks to the rise of digital health. This was certainly one not to miss, and most of the conference clearly didn’t – Mr. Bergstrom was told that attendance at some digital health booths was up 10x after his talk! Read below for all of the takeaways and some pretty amazing slides …
2. 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.
3. JDRF’s Dr. Aaron Kowalski gave an animated talk on why we need to think about other diabetes outcomes metrics and the tradeoffs between diabetes happiness (quality of life) and diabetes health. It’s always so valuable to hear Dr. Kowalski speak, but this 75-minute session gave him the chance to really dive in to issues about which he is passionate.
4. 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.
5. In the exhibit hall, we visited 21 diabetes technology booths, picking up notable updates along the way. One Drop is initiating a trial with MannKind and now has 350,000 registered users on its app; Glooko is piloting it’s new transmitter (picture below) in Sweden and will full-scale launch later this year; and we learned on Medtronic’s FAQ page that the MiniMed 670G pump and transmitters will be shipped first, followed by a separate Guardian Sensor 3 package between 30-90 days after the pump ships. We were also happy to see a strong digital health presence from the likes of Fit4D, WellDoc (first standalone booth), Voluntis (second exhibit hall appearance), and iSage Rx (exhibit hall debut!).
Diabetes Therapy Highlights
1. 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.
2. In an engaging morning session, Dr. Wendy Lane shared actionable advice on type 2 diabetes management in patients with high insulin requirements. Dr. Lane provided tips on the use of concentrated insulins in CSII and strongly advocated for the use of “insulin-sparing” adjunct therapies like SGLT-2 inhibitors and GLP-1 agonists to address postprandial spikes and control weight gain.
3. 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) as well as Xultophy. We very much agreed with the notion that Soliqua (insulin glargine/lixisenatide), as a very new product, would be able to circumvent the common misconception from patients that taking more medications signifies diabetes failure.
4. A second, absolutely packed Sanofi-sponsored symposium delved into the clinical challenges of optimizing basal insulin therapy in people with type 2 diabetes, featuring actionable pearls of wisdom from Dr. Nathan Painter, Ms. Teresa Pearson, and Dr. Guillermo Umpierrez. Next-gen basal insulin is so considerably better than basal analogs and we were happy to hear this session.
Big Picture Highlights
1. 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. His presentation was truly the talk of the town, with audience members commenting and Tweeting that it should have been a keynote! Dr. Gabbay helped lead our “Glycemic Outcomes Beyond A1c” gathering in Bethesda several weeks ago and he was also extremely highly regarded there.
2. 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, she said, considering all the progress that seems to be happening on this front). 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. Ms. Maryniuk emphasized the need to spread this message far and wide, to all players in diabetes care (providers, payers, industry, and the media). See our tweet and favorite slide from this very valuable session.
Diabetes Technology Highlights
1. BCG’s Chris Bergstrom: Let’s Get Digital. “Use Digital Health to reach more patients than you ever have. Basically, be superhuman.”
In a whirlwind keynote entitled “Let’s Get Digital,” BCG’s Mr. Chris Bergstrom, with help from videos of 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. He pointed out that the rate of technology adoption is only accelerating, and diabetes is seeing significant funding momentum – an estimated ~$450 million in VC funding in 2016 went to digital health & connected BGM, followed by ~$250 million for CGM and ~$200 million for non-invasive tech. Bigger players are also partnering across the board – Mr. Bergstrom noted partnerships for insulin companies (Sanofi/Verily, Novo Nordisk/IBM Watson/Glooko), glucose monitoring companies (Roche/mySugr, J&J/Samsung/WellDoc, Abbott/Bigfoot, Dexcom/Verily), and drug delivery companies (Medtronic/Glooko/IBM Watson, Insulet/Glooko). In connectivity, he was very positive on connected glucose monitoring, connected insulin pens/pen attachments (Timesulin – recently acquired by Bigfoot, GoCap, DataPen [we hadn’t heard of this one], InPen, and BD, and added that all big insulin companies are piloting and getting in on the game), and even connected pills (eTect, Proteus, Adhere Tech). In the remote support tier, Mr. Bergstrom highlighted Fit4D (diabetes coaching leveraging technology), HelpAround, and the subscription models emerging out of Livongo, One Drop, and mySugr. Notably, he shared that Livongo CDE’s responded to 110,861 out-of-range blood glucose checks this spring, almost 22,000 of them low. On a broader note, augmented reality (especially in diabetes education) will be a big deal in his view, and he showed a pretty compelling sentiment analysis that identified patient complaints in real time using social media. (See slides below.) 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! See our Detailed Discussion and Commentary below for more!
2. Adam Brown on Outcomes Beyond A1c, Why Time-in-Range Matters Today, and What Diabetes Care Might Look Like in A Beyond-A1c Era
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 21st 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.
3. Dr. Kowalski on Outcomes Beyond A1c – “My Life is Not Defined by a Three-month Average of Glycated Hemoglobin”
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, indicating 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 21st 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.
4. Dr. David Marrero On Health-Related Quality of Life
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.
Diabetes Therapy Highlights
1. GLP-1 Agonists: A Motley Crew of Agents, or a Cohesive Group with Class Effects?
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.
2. Therapeutic Options for Patients with High Insulin Requirements (and How Therapy Could Improve)
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.
3. Sanofi Symposium Outlines Soliqua’s Benefits in Patient-Facing Language
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) as well as Xultophy. 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.
4. Clinical Pearls for Optimizing Basal Insulin Therapy
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.
Big Picture Highlights
1. Dr. Gabbay on the Role of the Diabetes Educator in a Value-Based Care Model
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.
2. Call to Eradicate Judgmental Language from Diabetes, Starting with “Non-Complaint,” “Non-Adherent,” “Obese”
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.”
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.
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!
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 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 …
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’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 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 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 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’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.
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.
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’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).
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…
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 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’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.
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.
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!
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.
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 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.
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’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’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’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!
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.
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.
Detailed Discussion and Commentary
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 that 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 – although we don’t always see these two combined, it makes sense), 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 five to ten 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. Although some of these categories are diabetes-specific and others not, the point is still certainly that there’s big investing happening in digital and that diabetes is a poster child.
- 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 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. It's also worth noting that AADE President Ms. Nancy D'Hondt 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 (which we would certainly believe). 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.
- 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. It's also worth noting that AADE President Ms. Nancy D'Hondt 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!
- 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 hall 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). Indeed, 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. Cool!
- 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 (AADE Past President, Ms. Donna Ryan (AADE President Elect), 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
-- by Ann Carracher, Abigail Dove, Brian Levine, Payal Marathe, Maeve Serino, Adam Brown, and Kelly Close