August 17-20, 2018; Baltimore, MD; Days #1-2 Highlights – Draft

Greetings from Baltimore, Maryland! Below, you’ll find our extensive coverage from Days #1-2 of this fascinating meeting, including technology, therapy, and Big Picture highlights plus our exhibit hall coverage of over 30 booths. We’ve been excited to see outcomes beyond A1c movement in full-storm at AADE, as several presenters and booths have emphasized the importance of time-in-range and the limitations of A1c.

This meeting is always an excellent reminder of what “in-the-trenches” diabetes care looks like. For example, we attended an excellent Sunday afternoon session on using SGLT-2s and GLP-1s to reduce CV risk but thought we were in the wrong room for a moment – it was only ~one-third full a couple minutes before starting. Panicked, we ran to the ballroom next door: The doors to this packed session were being shut and new arrivals shunted to an overflow room. In reality, we had been in the right place the first time; the full session next door was actually on the relationship between mental health issues and diabetes. Of course, no one would argue that mental health is an insignificant issue in diabetes, but the relative attendance at these two sessions – the opposite of what we would expect at nearly any other diabetes meeting – reminded us that the day-to-day care of most people with diabetes simply has not gotten to using new meds to minimize CV risk: Patients and providers alike are dealing with more immediate concerns.

We’ll be back with Days #3-4 of the meeting shortly. Until then, read our preview for what’s in store!

Diabetes Technology Highlights

1. Educator Views on DIY AID ­– WIDE Range of Comfort! Type 2 diabetes CDEs Overview Features of OpenAPS, Loop; EU Medtrum CGM to Enter DIY Toolbox?

Type 1s/CDEs Ms. Brenda Weedman and Ms. Jessica Kirkman gave a sweeping overview of DIY closed loop technology to a roomful of peers, who had highly variable comfort and fluency with the subject matter. The variable baseline views on DIY and #WeAreNotWaiting were perhaps best-illustrated by two barometer questions from the speakers for the audience at the session’s outset: (i) What have you heard about DIY systems? (ii) What do you want to know about DIY systems? See a summary of answers in the table below. We also heard that the DIY community is working with Medtrum in Europe as a potential additional CGM option, and there is one family who has successfully hacked and incorporated an Animas pump into a DIY closed loop system.

• Loop updates/comments:

  • “Loopable” (legacy) Medtronic pumps are reportedly now being sold in Australia through their national insurance program.

  • “I thought for 15 years that my insulin:carb ratio was 1:15. The I was going low with Loop, and I wasn’t sure why. I was counting carbs…then, when I ran Autotune, it took my ratio to 12, then 10, then 9. The same ratio wasn’t concordant with closed loop settings like it was with open loop.” – Ms. Weedman

  • “I can bolus from my phone and Apple Watch. It’s a gamechanger. Even if the system didn’t do anything but that, I’d still wear it.” – Ms. Kirk

• OpenAPS updates/comments:

  • SuperMicroBolus (SMB) is an OpenAPS feature intended to prevent/blunt postprandial highs. The picture below shows the trace from a man who ate ~100 grams of carbs from pizza, and, thanks to SMB – each blue circle on the glucose trace represents a little bolus (0.1, 0.2 units of insulin – larger than a basal rate) – stayed between 90-160 mg/dl. Said Ms. Weedman, “I can’t do that with pizza in open loop after 34 years of experience.”

• We felt this quote accurately reflected the mindset of many DIYers with respect to risk: “What are we afraid of? When I was diagnosed in the 80s, I was on NPH, I didn’t have a BGM, pens, analog insulins, CGM, pumps. I had 9-1-1 and my parents. And I survived. And now I have all these tools, and I’m smarter – I was 17 then. So, why am I going to be afraid of with this?” – Ms. Weedman

Q: You said you mix Novolog and Fiasp 50/50 in your Loop – did you look at the pharmacologic interactions first?

Ms. Weedman: No. Fiasp is just aspart plus niacinamide, so it made sense. And some other Looper did it first, so I thought it’d be safe.

Q: You’ve convinced me to at least consider these. We do have one patient, a five-year old, whose dad is doing everything. I don’t understand what he’s doing, so I can’t help. And the other thing is de-skilling – at what point do we stop and say, ‘ok, you’re 12,’ what do we do at that point?

Ms. Weedman: The same decisions made for open loop pumping or injecting for children need to apply here as well. As they develop, they can be taught to take over this care.

Ms. Kirk: You can run it in open loop mode. You actuate insulin delivery, but you can see what it would recommend. See if you would agree with what it’s doing. Do you understand logic behind it? If you do, it will be successful. Just understand why the pump is making certain choices.

Q: With Medtronic out, and others coming, how will this fit in?

Ms. Weedman: I hope they copy everything the DIY community is doing. They could allow code to be open source, or use this code in pumps when they submit to FDA.

Q: Is this going to be for Animas pumps in the future?

Ms. Weedman: We have a lot of people wanting to Loop and not a lot of developers. I don’t know of anyone who’s taken up the Animas project. I did hear, anecdotally, an individual family looping with Animas, but they don’t want the notoriety or attention.

2. iPro CGM Study Shows High Time-In-Range Correlates with Lower Retinopathy (accepted to a well-known journal); Professional CGM Improves Outcomes and Reduces Healthcare Costs

Medtronic Director of Clinical and Medical Affairs Dr. Robert Vigersky underscored the importance of outcomes beyond A1c, alluding to a study accepted preliminarily to a well-known journal demonstrating an inverse relationship between time-in-range and prevalence of retinopathy in patients with type 2 diabetes. The large study was conducted in China, but other details were scant (since the article is not yet published). Still, this seems exciting for validating time-in-range, especially after Dr. Roy Beck’s compelling analysis presented at ADA showing high correlation between time-in-range in DCCT (derived from seven-point BGM profiles) and microvascular complications. We’re not sure for how long patients wore CGM in China (retinopathy takes some time to develop), how frequently they wore CGM (the whole period vs. a week here and there), the retina health of the population at baseline, and other factors, all of which would affect the interpretation of the data. Dr. Vigersky noted the results represent a “first step” towards evidence that time-in-range can predict outcomes. He postulated that, “ultimately, A1c is going to go away” in favor of time-in-range. The recent consensus definitions for metrics like time-in-range will allow for better comparisons of drug trials, while patients across the board (type 1s, type 2s on insulin, and types 2s not on insulin) have indicated that time-in-range is a very important outcome to them (Runge et al, Clinical Diabetes 2017). As Dr. Vigersky put it, “Our patients get it.” We can hardly wait to view the data from this latest study examining retinopathy (Dr. Vigersky expects the results will be published in the coming months) and were thrilled to see such a substantial portion of the product theater devoted to explaining the value of time-in-range.

• Dr. Vigersky explained that not only does professional CGM have the potential to reduce “clinical inertia” and improve patient outcomes, it also has been shown to reduce healthcare costs in patients with type 2 diabetes. He cited a retrospective claims analysis of 6.2 million insurance claims recently published in the Journal of Medical Economics associating professional CGM with a 0.5% reduction in A1c within one year of use, as well as $3,327 in annual savings for patients with a therapy change following professional CGM use. He described how primary care physicians are overwhelmed, noting that there are 640 unique type 2 therapy combinations and A1c alone is insufficient in instructing clinicians on the optimal treatment path. This confusion, Dr. Vigersky explained, results in 40% of patients receiving no change in therapy despite having an A1c >7% for over a year. Dr. Vigersky believes professional CGM can help combat such clinical inertia – and he had the evidence to back it up: A 2014 study found a 3.5x increase in therapy change associated with professional CGM use (the study was retrospective, so it could be that provider-patient combos likely to try professional CGM are also more likely to actively modulate treatment). We think professional CGM bears enormous promise globally, especially in the prediabetes and type 2 diabetes populations in lower-resource settings. We’re reminded of an especially impressive study from ADA, which found that just one 14-day session of Abbott’s FreeStyle Libre Pro – with an interpolated provider visit on day 7 – significantly improved type 2 glycemia in India (a whopping +9 hours per day in range). Perhaps the biggest need in this field is more studies of how to roll out professional CGM in type 2/prediabetes – What’s the right cadence? What’s the right model for analysis? What is possible to do remotely? How might reimbursement and/or pricing be simplified or improved to increase use of professional CGM in the clinic?

3. Senseonics Eversense standing-room-only product theater: three paths to reimbursement; Human factors done on NP/PA insertions; Nice marketing vs. other CGMs; Medicare?

In a completely packed, standing-room-only product theater before the start of AADE, Senseonics debuted the 90-day Eversense CGM at its first AADE following June’s FDA approval and first insertions earlier this month. The most interesting comment came in Q&A, where the company shared it has three avenues to get patients reimbursed for Eversense: (i) traditional DME path; (ii) pharmacy channel; and (iii) a CPT code that bundles the procedure with the cost of sensors. “It’s going to be determined by the payer, and we can work with you.” We hadn’t realized pharmacy was also possible for Eversense, and this reimbursement flexibility seems like a nice advantage for Senseonics – especially the bundled CPT code. Reimbursement is obviously a major gating factor to scale, as Senseonics has only announced coverage with one payer (BCBSNJ); otherwise, patients will need prior authorizations to get covered on a case-by-case basis. Of course, scale is also contingent on training enough healthcare providers and getting them excited about the procedure.

• Eversense was only approved for physicians to insert the sensor, though Senseonics has completed the human factors allowing NPs and PA to do the procedure. The company is “eagerly pursuing this avenue,” though no specific timing was shared on a potential launch. Expanding the current label in this way would be a huge advantage – according to CMS data from 2010, there are a significant ~106,000 practicing NPs and ~70,000 practicing PAs. Even if only a fraction are working in diabetes, this will certainly expand the funnel of HCPs that can insert the sensor – a gating factor to adoption. 

• Senseonics will add the Ambulatory Glucose Profile report to its own software “later this year,” a great win for data standardization and one that joins Abbott, Dexcom, Glooko/Diasend, and Roche. We heard at ATTD in February that Medtronic has reportedly licensed AGP, but do not believe that has launched yet or been publicly confirmed by Medtronic. Eversense data will also flow into Glooko “later this year,” on par with July’s partnership announcement.

  • We love that Senseonics’ mobile app allows users to see CGM statistics without having to go to a separate CGM data analysis app (e.g., Dexcom Clarity, Medtronic Sugar.IQ). Keeping the analysis app separate does allow for more iteration and less regulatory concern within the core CGM receiver app, it also requires marketing and building awareness of a separate app.

• In a question about Medicare coverage, something we hadn’t thought of came up: how will Medicare handle the no-receiver, smartphone-only, implanted Eversense CGM? Obviously step one is obtaining a non-adjunctive label claim from FDA, which Senseonics plans to file within the next month alongside a move to one calibration per day (2Q18 call). However, the company will then have to navigate how Medicare will categorize the device – the established Part B path under DME seems less likely, given the lack of a receiver or another component that lasts three years. (Both Dexcom and Abbott rely on this via the DME receiver/reader.) Presumably Senseonics could go for Part D (pharmacy), like Insulet’s Omnipod, or some kind of bundled procedural reimbursement under a new pathway. “We are confident that Medicare sees the value in getting patients access to a technology that drives better adherence and compliance, but it’s not going to be immediate coverage out of the box.”

• In a very crowded US CGM landscape, Senseonics is doing a nice job marketing the differentiators of its first-gen product in the US, including: (i) the reduction in “day 1’s” to once every 90 days (relative to once every 7-14 days for other CGMs); (ii) the elimination of self-insertions (and therefore less training for educators); (iii) the “gentle” silicone-based adhesive, which was handed out to attendees with the on-body transmitter drawn on top of it; and (iv) the on-body vibrations for highs/lows via the transmitter.

• A slide that also caught our eye was an updated Senseonics accuracy comparison to other CGMs – see below – which still looks favorable for Senseonics, in line with our initial view at March’s FDA Advisory Committee. The slide excluded Dexcom G6’s accuracy of 83% within 15/15 (labeled “NA”), which is not summarized in the G6 user guide but was shared at Dexcom’s ADA Product Theater. (For context, this is from the smaller n=62 automatic applicator study, which is summarized in table 10 in the user guide but only includes 20/20 accuracy.) Senseonics’ slide also did not use G6’s marketed MARD of 9.0%, which uses the aforementioned auto-applicator study and is only shared in table 10 of the G6 user guide. Senseonics is using the MARD of 8.5% from PRECISE II, which is better than the 9.6% seen in the fairly similar PRECISION study; this is reasonable in our view, given that Dexcom is also using the lower MARD of its two G6 pivotal accuracy studies.

  • We wonder if Senseonics will go for iCGM labeling, as its accuracy should meet the special controls. This could give it more interoperability flexibility, especially with Tandem and Beta Bionics both using Dexcom’s G6 iCGM for their AID systems. Interestingly, an iCGM filing did not receive an update on Senseonics’ 2Q18 call.

4. Case Studies of Peds/Teens on 670G (+12-13 Hrs/Day In-Range); 97% of Peds Pivotal Participants Stayed on 670G After Trial; Peds Endo Tips for 670G use (Cal Frequency, Exercise, ICR, Temp Targets, Gastroparesis)

Pediatric endocrinologist Dr. Kevin Kaiserman and Medtronic’s Ms. Zuly Hernandez shared astounding case studies demonstrating the efficacy of the MiniMed 670G hybrid closed loop in pediatrics. As a reminder, FDA approved the system for use down to age seven in June following a 7-13-year-old pivotal trial (0.4% reduction in A1c from baseline 7.9% and +2 hours/day improvement in time-in-range). We learned during the symposium that 102 of the 105 peds pivotal enrollees (97%) continued to wear the system after the trial ended, a strong vote of confidence for usability and value in a population that certainly needs help. Dr. Kaiserman’s Q&A with the audience after the talks revealed a deep understanding of how to use the system, complete with tips for insulin:carb ratio, temp targets, calibration frequency (even if the system demands it, wait at least 30 minutes between calibrations), gastroparesis, and exercise.

• Dr. Kaiserman told of a young, 6’6” male basketball player who participated in the 670G pivotal study at age 12, boosting his time-in-range (71-180 mg/dl) from 32% to 82% (+12 hours per day) while dropping his A1c from 7.7% to 6.6%. These improved glycemic metrics have been maintained for two years, and oh, and by the way, he eats an average of 691 carbs per day! Most of the improvements during the 670G pivotal came during the overnight period, where fear of hypoglycemia had previously caused him and his parents to let his glucose soar overnight. His glycemic variability also decreased, and six months after auto mode started he was spending just 2% <70 mg/dl, and 0% <54 mg/dl. “The system allowed him to pursue his goals, participate in very-high-level basketball. His parents, who were up all night chasing his glucoses, are sleeping now, and they’re all trusting the system. He has better overall control, even going from a 12-year-old to a 14-year-old adolescent, he trusts the system more, and he is pursuing his basketball dreams.” Notably, the patient wears his 670G while he plays sports. 

• Ms. Hernandez presented the case of a 15-year-old male, an “active young guy, very erratic, skateboards, plays football – your typical teen” who went from MDI to 670G and saw his time-in-range climb from 31% to 87% (+13.4 hours/day) in a matter of three months. He remarkably had no hypoglycemia either in manual or auto mode, and saw his time >180 mg/dl and >250 mg/dl shrink from 31%->11% (-2.4 hours/day) and 32%->2% (-7.2 hours/day), respectively. Wow – shaving off seven hours per day over 250 mg/dl is extraordinarily compelling. What’s more, slashing hyperglycemia was actually achieved with a lower total daily dose of insulin (he went from units per day in the ~40s to units per day in the ~30s). This stark turnaround in glycemia didn’t happen immediately, as it took three months to acclimate him to the 670G and get him in auto mode – at first, stigma led him to take his pump off for 4-6 hours per day at school.

  • The 13.4 hour/day improvement in time-in-range is astounding, but also must be interpreted in the appropriate context. The patient was on MDI prior to starting on 670G, and it’s possible his time-in-range was greater than 31%. Given that the baseline for this comparison was 670G manual mode – when he was disconnecting and not bolusing for 4-6 hours each day – the incremental benefit of auto mode may be overstated in this particular case. However, the improvement here is quite phenomenal and shows how much better young type 1’s are going to do on AID.

Questions and Answers

Q: We have a lot of adults on 670G. The challenge we’re facing is we’re pretty aggressive on active insulin time. How far can you go with that? The second challenge is temp target – five or six of our clients still get hypoglycemia and many alerts overnight, so we have them use the temp. Even with increased insulin activity time, how soon before physical activity should we be them to set the temp target.

Dr. Kaiserman: One of the keys to 670G is optimizing insulin:carb ratio, it has the greatest impact on outcomes. Active insulin time is a small component, since it really only relates to correction doses. You can set active insulin time as low as two hours for 15-minute increments, and look at how they’re responding to correction doses. If they’re not coming down – the correction dose drives down to 150 mg/dl, then the basal drives down to 120 – so if they’re not coming close to that target, then you can shorten active insulin time. If they’re dropping too low after a correction, then it may be that the active insulin time too short. Generally speaking, people are making some adjustments there. Some adult healthcare providers are finding that reducing active insulin time helps – it’s not automatic, but look at it – most patients ended up around three hours in the pivotal. You can go as low as two hours.

Regarding your comment about lows: The recommendation is to start the temp target one to two hours prior to exercise. Keep in mind where sensor glucose is before exercise. Traditionally, people take carbs before exercise, but if you raise sensor glucose above target, you’ll be given more basal insulin and you’ll have lows. So loading up on free carbs before exercise can actually backfire – basal goes up, and you’ll go low. If you’re at 75 mg/dl going into exercise, then take carbs. If you’re 140, 150 mg/l before exercise, you don’t want to load up on carbs. 

Q: We’re finding a lot of our clients are getting alarm fatigue due to the demand of calibrations. We’re having a lot more people say they’re shutting off auto mode, and they like the suspend before low setting better. Is there any way to reduce alarm fatigue when they’re already calibrating four times per day correctly?

Dr. Kaiserman: This has been a major issue with sensor adoption. I generally recommend three calibrations per day – when they wake, before sleep, and once in between – but they don’t want to calibrate more than once in a 30-minute period. Even if an alert comes up, you want to train patients to wait 30 minutes. That alone will reduce the issue of repeat calibrations. One of the key things is that as you optimize the rest of therapy – get to right insulin:carb ratio, getting the carbs in before eating – they’ll see fewer alarms in general. One of the keys is to resist more frequent calibrations. That should help, and we’ve seen it reduce some of those issues.

Q: For patients with gastroparesis, they need to bolus before eating, but they’re not doing that a lot for fear of hypoglycemia. What do you recommend for them on 670G?

Dr. Kaiserman: I definitely want to keep all patients in auto mode as best I can. The goal is to figure out how to optimize their therapy. We still want them to bolus a bit before meals, but they may have to do a second bolus as well. The risk for hypoglycemia should be mitigated by automated basal. The therapy is to help adjust and mitigate excursions. It’s about getting as close as you can with a bolus close to the 120 mg/dl target and letting the auto basal keep them there. Figure out a bolus in all clinical situations to get you closer to that target, then let the basal do the rest. Auto basal should also help to reduce fear of hypoglycemia. Start with small boluses, then work your way up. You want to give as much insulin up front, generally if you can, in all clinical situations.

Q: How do you go about optimizing insulin:carb ratios? What about disconnecting for sports?

Dr. Kaiserman: Generally, you’re adjusting insulin:carb ratios by 10% at a time, in that range, depending on postprandial control. You can use the “rule of 450” as an estimate, but it’s just an estimate, not a rule. Trying to optimize postprandial control, people are often afraid of postprandial hypoglycemia, so they tolerate more hyperglycemia. As you reduce the risk of postprandial lows, you’re not trying to be aggressive but trying to be appropriate. Sometimes even making small adjustments, going from an insulin:carb ratio of 10 to 9.5, you have a lot of control, but you really want to get the insulin:carb ratio to a place where you’re giving an appropriate bolus prior to eating – 5-10 minutes prior to all meal and snacks – and trying to get to a place where you’re optimizing that postprandial number. If you’re close to target after meal time, you really will maintain close control in that post-meal setting.

I deal with all kinds of athletes, pro, college, Division 1 – more people are wearing the system even when they wouldn’t before – including in contact sports – because they want auto mode. They’re happier with outcomes when they stay on the system. If you are disconnecting, it’s the standard pump recommendations, but it is recommended to suspend insulin delivery because it is calculating future doses based on past total daily dose. But I’m finding far more patients choosing to stay on the 670G therapy during sports.

5. Insulet Working “Really Hard” on Securing Pump Control from Phone (Remote Bolus); Cadence of New Products for Next Three Years

Medical Director/SVP Dr. Trang Ly spoke at a Dash product theater reminiscent of those at Keystone and ADA, but the biggest update came in Q&A: She confirmed that controlling the Pod from the phone is on the roadmap. In response to a roundabout question getting at timing for a feature allowing bolusing from the phone, Dr. Ly responded, “We’re working hard on that, like really hard. I can’t tell you any time frame, but it’s very high on the list.” This development is not surprising, of course, since we learned in May that both Insulet and Bigfoot are launch partners with Google for Android Protected Confirmation, which will enable secure insulin pump control. Wearing only an on-body pod and controlling it from a user’s own smartphone (no PDM needed) would be a truly compelling form factor. In the current Dash iteration, patients can use the Omnipod View app to discreetly monitor PDM activity, but instructions cannot be sent from the app to the pump. (As a side note, Dr. Ly’s demo of View’s “Find my PDM” feature drew oohs and ahs from the audience, though some initially thought it was a smoke detector.) At this point, SOOIL’s Dana pump (outside of the US) is the only cleared pump available, to our knowledge, that does allow for direct smartphone control (no bridging device needed). During the course of Q&A, Dr. Ly also confirmed that the current Omnipod PDM (pre-Dash) will be phased out “eventually, but not anytime soon” and that the 80,000+ item CalorieKing library on the PDM will not update automatically, but it’s “something the team is looking at.”

• Dr. Ly positioned Insulet’s pipeline as a cadence of new products, with launches every year for the next three years. We hadn’t thought about it that way, but indeed, Dash will launch broadly in 2019, the Horizon hybrid closed loop system could launch in late 2019-mid-2020, and the Lilly-partnered U500 and U200 Omnipods are slated for 2019 and “end of 2020 or 2021,” respectively (per Insulet 2Q18).

• The Omnipod Demo app gives potential users a taste of the Dash PDM, a guided tour of its features, and links to educational resources – this sounds identical to Tandem’s t:simulator. We could not find it on the app store yet, but presumably that will change as the full commercial launch nears. Given that pump decisions lock patients in for ~4 years, this pseudo-test drive will be a big win for patients, providers, and payers.

• Pod University (Pod U; Myomnipod.com/PodU) will be available shortly. The resource offers short, digestible, educational series to support teaching sessions between HCPs and patients. Dr. Ly flashed “Blood Glucose 101” and “Nutrition 101” on the screen, and asked for feedback from attendees to ensure the subsequent resources are useful. Insulet’s “Nutrition 101” uses the government’s MyPlate messaging, which recommends ¼ of the plate filled with fruit, ¼ filled with grains, and a serving a dairy – easily 60 grams of carbs per meal. We understand the need to use vetted materials, though wish there was a greater awareness of lower-carb approaches too.

6. Tandem t:slim X2 Basal-IQ with Dexcom G6 “Commercially Available As Of This Week”; Dr. Daniel DeSalvo’s Pediatric Glycemic Goals

During a Dexcom product theater, Baylor College of Medicine’s Dr. Daniel DeSalvo highlighted that Tandem’s t:slim X2 Basal-IQ (predictive low glucose suspend) with Dexcom G6 integration is “commercially available as of this week” – see our coverage. Dr. DeSalvo highlighted the G6’s iCGM designation, which helped keep the integrated pump up to date with the latest sensor – as a reminder, the pivotal trial and FDA submission for Basal-IQ used G5 (FDA technically approved both G5 and iCGM compatibility, but Basal-IQ will only work with G6 for simplicity on Tandem’s end). We’re thrilled to hear Basal-IQ is now on its way into the hands of the first patients, marking the first automated insulin delivery device approved with no-calibration CGM, the first pump compatible with an iCGM sensor cleared for interoperability, and the first AID algorithm to be launched via software update without needing new hardware (and at no cost for current users!).

• Dr. DeSalvo shared that, following a quality improvement project recently implemented at Texas Children’s Hospital, over 90% of his privately-insured patients start CGM within three months of type 1 diabetes diagnosis. He believes CGM is “approaching standard of care,” strongly recommending initiation of CGM at diagnosis. In fact, each patient is paired with an educator at diagnosis for immediate support.

• Dr. DeSalvo shared his “Dr. Dan’s Rule of 7-5 for Pediatrics” outlining the glycemic goals he sets for his young patients: (i) A1c <7.5% (in line with ADA recommendations); (ii) average blood glucose <175 mg/dl; (iii) standard deviation <75% (ideally less than mean blood glucose divided by three); (iv) <7.5% time <70 mg/dl; (v) <2% time <54 mg/dl; and (vi) >75% time-in-range – a “bonus” according to Dr. DeSalvo, as this time-in-range is difficult to achieve in pediatrics.

• Dexcom’s Ms. Christine Pospisil underscored the importance of dosing with arrows, but cautioned that not every patient will be immediately ready for this degree of self-management. She advised the following: (i) ask patients how they’re making adjustments; (ii) ask patients if they’ve made changes to their insulin dose, insulin dose timing, or if they use temporary basal rates; (iii) consider that while frequent bolus overrides may indicate a need for adjustments, it also is a “good sign” that patients may be ready to dose off trend arrows; (iv) give “permission” to patients to make real-time changes; and (v) set actionable alerts to avoid alert fatigue and keep checking alerts at every appointment.

7. Digital CDE Fireside Chat: Stories of How Remote CDEs Support face-to-face CDEs; Welldoc Looking for Human Touch?

A “Fireside chat” with Welldoc’s Ms. Janice MacLeod, Livongo’s Ms. Toby Smithson, One Drop’s Ms. Rachel Head, and Tandem’s Ms. Molly McElwee Malloy (moderator) illustrated the clear value-add of digital coaching (“CDEs at sea”) in complementing the work of traditional CDEs (“CDEs on land”). Ms. Head told the story of a man who, 1.5 years ago, got diagnosed with type 2 diabetes with an A1c “pushing 12%.” He was told he needed to start insulin right away, but he bargained for more time to improve his glycemia. He started oral meds and found One Drop, and proceeded through the One Drop curriculum, learning the basics of diabetes management along with tips and tricks for putting behavior change into action. Ms. Head communicated with him in a “hands-on, accessible, near-daily” fashion, helping him to implement a walking/exercise routine, solidify healthy eating habits, better manage stress, “you name it. We cover everything.” Less than a year later, he was off orals and his blood pressure medicine completely. By this time, he had lost substantial weight and his A1c was below 6% in less than a year. “He was just blown away. And happy stories like this just roll in,” Ms. Head said. Ms. Smithson also had a case study: A woman was diagnosed with diabetes in January, and she scheduled her first coaching session for right after her first CDE meeting. She had a call with Ms. Smithson, who took the goals she set with her CDE, who helped her fill in the gaps and explained unclear concepts. At first, they communicated weekly, then every other week, and then once a month. The woman went back to her “on land” CDE three months later, and she reported that everyone was jumping around the office with excitement, showing others her numbers. Ms. Smithson noted the ability to remotely fill in the gaps when the patient couldn’t be in the office with her CDE due to reimbursement and life. The message was captured well by Ms. Head: “We can be in someone’s pocket at the grocery store, at the gym, in their house – when these things come up. Behavior change doesn’t necessarily take place in a 30-minute clinic visit. It’s non-stop.” According to Ms. MacLeod, Welldoc’s automated coaching has a different manner of changing behavior: “I can think of a really good example of an individual who had been saying, ‘diabetes doesn’t make any sense.’ With BlueStar’s coaching and prompting, he actually changed his eating habits. He knew BlueStar would ask him to check post-meal blood glucose, so he started making better food choices because he knew BlueStar would check in – something that’s ok for the app but not for a spouse to ask. The patient ultimately started eating better, lost weight, and his provider was able to reduce the insulin dose.”

• Ms. MacLeod shared that Welldoc is evaluating ways to expand on its fully-automated coaching by weaving in the right member of their care team: “We’re automating what can be automated in terms of coaching; if you’re in hypoglycemia, the app provides that coaching right in the moment. We’re working on – and we believe we can crack the nut – identifying the right level and timing of a human touch point, bringing in the right person from the patient’s own care team at the right time. Could it be a peer coach? Could it be a social worker? Could it be a CDE or coach or care coordinator who could bring the pieces together? Do we need a prescriber? Or could a CDE practicing at the top of his/her license actually be the one to make sure the treatment is optimized and leading other members of the team? We’re learning and don’t pretend to have all of the answers yet, but it’s an exciting space to explore.”

  • We wonder how much competitive forces are pushing Welldoc in this direction, given what peers Livongo, mySugr, and One Drop are doing with a mix of automated/human coaching. Getting that combination right will help mix scalability (with software) and accountability (with a human) …

Quotable Quotes

• “People with diabetes are given 1,000 tasks per year for diabetes management. Digital health can help us not only see the numbers, but also to help them in their world as well. As a Livongo coach and CDE, I am meeting people literally where they are, all on the phone. Sometimes they are driving, but literally meeting them where they are, maybe at the park, watching their kids play. It’s something to think about – truly meeting people where they are. Also, we serve as the in-between to connect to the on-land CDE.” – Ms. Smithson

• “In the outpatient setting, there are a ton of hoops to continuously jump through regarding access to patient care, and it was maddeningly frustrating.” – Ms. Head

• “We need to put thoughts and energy toward how we can improve the health of a population in the most cost-effective way, without obsessing about the reimbursement. I think the future will be very soon upon us where the payment is the reality.” – Ms. MacLeod

8. BDC’s Laurel Messer: MiniMed 670G is Finally Reaching the Masses; Sensor Health as “The Most Important”; Tips and Tricks for Success on 670G

In a session dedicated to best practices for the successful initiation of Medtronic’s MiniMed 670G hybrid-closed loop system, we were pleased to hear Barbara Davis Center’s Ms. Laurel Messer claim: “We’re really starting to see a lot of patients using the 670G now.” As she explained, there’s often a lag between commercial availability of novel technology and actual uptake in clinics – especially in pumps, where the insurance cadence is on a maddeningly long  four-year cycle. The 670G is no exception (made even more challenging by sensor shortages restricting access for months), but we’d agree that the tides are changing in a hurry – as of Medtronic’s 1Q18 call in May, over 70,000 patients were actively using the 670G and 100,000 systems had shipped. We imagine that number has continued to climb, and hope to know for sure tomorrow on the company’s F1Q19 (2Q18 call). While Ms. Messer, along with her fellow presenters Ms. Cari Berget (Barbara Davis Center) and Ms. Marie Schongar (Albany Medical Center), extolled the benefits of 670G and shared positive user experiences, all three acknowledged that the system is not perfect for every patient, requiring careful patient selection and strategic tips and tricks (see below for our favorites). In response to a question regarding a hack for extended boluses, Ms. Messer admitted that “this is a system with few workarounds.” Specifically to deal with meals, she recommended that patients either split their boluses manually (one bolus up front and one bolus later to deal with high-fat, slower-absorbing meals) or adopt “a mental threshold” with a greater tolerance of post-meal hyperglycemia in exchange for dramatic improvements in overnight and fasting glycemia. Clearly this is an area Medtronic needs to improve as, as basal-modulation is really well-suited to covering high-fat meals (certainly for DIY users). Ms. Messer is truly a wealth of knowledge on this system – see her commentary from ADA 2018 and CDTM 2017 for more.

• Ms. Berget emphasized sensor health as “the most important piece to the puzzle.” She underscored that calibrating 3-4 times/day is optimal (not more, not less) and that patients should be advised not to calibrate during hypoglycemia, hyperglycemia, exercise, or periods of glycemic variability. It will be fascinating to see how Tandem’s Basal-IQ competes with 670G – zero fingerstick calibrations is a huge advantage, though obviously for now Tandem only has the bottom half of closed loop in Basal-IQ (PLGS).

• Ms. Shongar reminded attendees to focus on outcomes beyond A1c, highlighting specific goals for time-in-range and time spent in hypoglycemia. She noted that time-in-range >70% is ideal, and that patients should aim for <3% time in hypoglycemia (50-70 mg/dl) and <1% time in severe hypoglycemia (<50 mg/dl). She also suggested a goal of >80% of time in Auto Mode and >85% sensor wear. We’re so glad to see the discussion shifting further from the merits of outcomes beyond A1c towards implementing them and establishing benchmarks.

• Ms. Berget shared two tips to increase time in Auto Mode: (i) give a correction bolus if the sensor glucose is high, as prolonged hyperglycemia will result in exiting Auto Mode; and (ii) perform a fingerstick every night before bedtime, providing an opportunity to calibrate and correct a high blood glucose, if necessary.

9. Flying Blind Without Data Downloads; A1c as a “Rudimentary” Metric

Ohio State’s Ms. Eileen Faulds called for the diabetes data download to be included as part of a patient’s vital signs, echoing similar sentiments from UW’s Dr. Irl Hirsch. As she put it, “if you’re trying to manage diabetes and you’re not using data downloads, you’re flying blind.” Importantly, she emphasized the limitations of assessing a patient’s A1c alone, characterizing it as a “rudimentary” metric providing a “ballpark picture.” We were delighted to hear Ms. Fauld’s focus on outcomes beyond A1c, especially given the overwhelming presence of diabetes educators in the room – teaching the clinical community and building awareness of CGM is going to take many years. Beyond using the data download to evaluate glycemic variability, Ms. Faulds also advised attendees to consider its potential for better understanding patient adherence and educational needs.

• Ms. Faulds recommended Glooko and Tidepool, praising both offerings’ ability to integrate data from multiple devices into one simple display. Ms. Faulds finds Glooko’s “Best Day” feature particularly instructive – not just in motivating patients but also for her own clinical practices. As she explained, if a best day is achieved only with herculean effort on the patient’s part (i.e. copious fingersticks, constant bolus overrides), it’s probably an indication that the clinician should reevaluate the patient’s insulin and/or pump settings. We love the emphasis on leveraging the data download and finding Bright Spots to foster a more productive patient-provider relationship. Perhaps the biggest challenge facing all the companies is digging slightly deeper – what happened on a “best day” that made it unique? How can a patient replicate those conditions?

Diabetes Therapy Highlights

1. Dr. James Gavin: “We’re Treating by Policy, Not Physiology”; Says Metformin Needs to Be Used More Effectively and Warns Against Stepwise Approach as a Barrier to Appropriate & Prompt Treatment Intensification

Speaking to considerations for selecting therapy “after metformin,” the great Dr. James Gavin predicted increased use of SGLT-2 inhibitors as second-line therapy, broader utilization of GLP-1 agonists, and even a future “core therapy” of metformin/SGLT-2/GLP-1 combinations with or without low-dose pioglitazone. This talk was an absolute tour-de-force spanning pathophysiology, outcomes trials, and treatment algorithms, with a particular focus on CV outcomes. To kick things off, Dr. Gavin presented a patient case: A 48-year old, previously undiagnosed male with an FPG of 201 mg/dl and A1c of 8.7%, BMI of 31 kg/m², and eGFR of 74 ml/min/1.73 m²; with a hectic lifestyle, he needs a simple treatment plan, and very strongly does not want to take injections. When the audience was surveyed, 67% opted to start him on metformin and check back in three months, while the remainder also included a GLP-1 agonist or SGLT-2 inhibitor in the treatment plan (split ~50/50). In Dr. Gavin’s assessment, metformin isn’t wrong: It’s what’s in the guidelines. But he also emphasized that this case puts into focus the treatment needs not currently being met, urging the audience to think more often and more clearly about individual patient pathophysiology, optimal sequencing of treatment, and even the shortcomings of current treatments. With this, Dr. Gavin added his two cents to the ongoing metformin debate: “Metformin doesn’t hold people where we need them – but it’s good, we keep learning more about it, and it’s basically free. We can keep researching it, but it’s going to be around. Our challenge is: How do we use metformin most effectively? […] We’re treating by policy, not physiology. It’s critical we understand the complementary nature of all the treatments available, and I suggest we need to be more flexible in the way we think about this.” In his view, it seems, the problem isn’t the use of metformin, but the over-reliance on metformin for too long; it’s the first step in the dominant stepwise treatment algorithm that comes with the steep price of periods of detrimental hyperglycemia. Bringing CV outcomes into the equation, Dr. Gavin showed that people with diabetes aren’t being adequately treated, and it’s translating into poor CV health: Across A1c, blood pressure, and LDL-C, ~50% of patients in each category are meeting goals. Less than 20% of patients are meeting targets in all three categories, which he says flies in the face of diabetes’ dynamic pathophysiology and simply isn’t going to cut it on changing CV outcomes. So, what’s the alternative? Dr. Gavin focused most heavily on the role of SGLT-2s as post-metformin therapy, due to the class-wide benefits on weight loss, likely renal-protection, and an array of cardioprotective effects – all in an oral agent with a variety of metformin and DPP-4 inhibitor co-formulations. In his view, SGLT-2s are bound to become a more common first-choice after metformin, despite more intermediate effects on glucose. He also argued that the similar benefits of GLP-1 agonists, in addition to preserving beta cell function, will drive these agents toward earlier use, then presented the EDICT and QATAR studies as evidence of the benefits of initiating combination therapy earlier in the course of disease.  Indeed, we think the field and guidelines would benefit enormously from earlier and more aggressive use of combination therapies, as longer-term evidence builds in favor of these approaches, but we think this will take some time, including some major shifts in the healthcare systems globally to make combination strategies commonplace. While monotherapy is used only infrequently in many cancers today, other therapeutic areas don’t have exactly the same challenges (many doctors would rather titrate monotherapy, many HCPs do not view expanded time in range or lower A1cs as their responsibility, many HCPs do not weigh the benefits of one co-pay and one dose as positively as many patients might, etc.)

• On glycemic targets, Dr. Gavin laid out a situation in which the field is missing the forest (CV outcomes and morbidity) for the trees (glucose lowering and A1c). He explained that, long before the development of hyperglycemia and especially microvascular complications, the pathophysiology of insulin resistance underlying macrovascular complications is well underway (Dr. Ralph DeFronzo recently outlined this process at Keystone 2018). In his view, we’ve “handcuffed” ourselves to the concept of glycemic control and A1c lowering, and the field has also focused too heavily on defining what “control” of glycemia means. In fact, an A1c goal of <7%, he says, is relatively conservative and certainly not physiologic, but rather an accommodation that has been made in guidelines because it is what could be achieved in clinical and outcomes trials: “It’s good, but it’s not the holy grail.” While microvascular complications are consistently responsive to reduced hyperglycemia, macrovascular complications are less so; clearly, there are other things HCPs need to focus on to improve CV outcomes.

• We heard a bit of chatter after the session about the cost of these medications. Our sense is that a fair number of attendees don’t actually see patients (or at least many patients) who are taking GLP-1s or SGLT-2s; among those who are familiar with the impressive effects these classes have, they decry that high co-pays keep them out of reach for many. Despite the existence of copay cards and patient assistance programs, this meeting has made it abundantly clear that the best diabetes medications simply remain financially out of reach for most – we wonder how many are actually trying to use the patient assistance programs (diaTribe recently wrote about these – “How to Get Drugs For Free”)? Some HCPs have also told us “my patients never quality for patient assistance” (one even told us he throws away all the forms) – there must be better ways to collaborate since we do not hear complaints about the costs of heart attacks, strokes, kidney disease, dialysis, amputations, blindness, etc. We hope and expect that this will change as patient advocacy builds – we cannot only wait for medicines to “go generic” particularly since many generics companies are being derided for their high prices and the ways in which they inhibit access. To be sure, we would love to see more manufacturers and other industry stakeholders invest more in improving access and affordability directly for patients although admittedly we don’t know much about following this work. We welcome comments and suggestions on this front.

2. What’s New in Diabetes Meds? Pharmacists Highlight Innovation in GLP-1 from Ozempic, Oral Semaglutide, BCise Autoinjector; Audience Thrilled About Next-Gen Glucagon Candidates; Focus on Biosimilar Insulins

In a standing-room-only session on new and coming medications, Cleveland Clinic’s Dr. Diana Isaacs and University of Missouri’s Dr. Andrew Bzowyckyj (both PharmD’s) offered a rundown on diabetes therapy. Below, we highlight the most notable, high-level takeaways from each class they covered.

• GLP-1 agonists: Dr. Bzowyckyj characterized Ozempic as a real breakthrough in GLP-1s, highlighting the superiority this newest class member has demonstrated on both A1c lowering and weight loss against other GLP-1s, most notably Trulicity in the SUSTAIN 7 trial. While the product is not (yet) indicated for CV risk reduction or weight loss, she drove home the point that it’s not a “me too” drug – it really is better than what was out there before. However, based on the 76% increased risk for retinopathy seen in SUSTAIN 6, she says providers should exercise caution in giving Ozempic to people with high retinopathy risk. In the pipeline, she touched on Novo Nordisk’s phase 3 oral semaglutide: An NDA is currently expected in 2019, and Dr. Bzowyckyj focused specifically on PIONEER 1 results in explaining that A1c lowering is quite dose-dependent for this first-ever oral GLP-1, also emphasizing that the highest dose is necessary for significant weight loss. Also in the pipeline, Dr. Isaacs addressed ITCA 650, Intarcia’s implantable exenatide mini-pump, which offers 3-6 months of subcutaneous GLP-1 release; she noted that, while Intarcia had a presence at AADE 2017, the company is absent from this year’s meeting following the September 2017 CRL for ITCA 650. Indeed, despite reflecting positively on results from ITCA 650’s pivotal program and the potential for this product to solve some adherence issues, she expressed uncertainty about where the company stands on resubmission (we understand that they’re diligently preparing a new NDA). She also floated the idea of using the same mini-pump system for other molecules, suggesting the idea of continuous amylin administration ­– we’ve certainly noted increased interest in amylin of late, across type 1, type 2, and obesity.

• Glucagon: The most “oohs and ahs” came when Dr. Isaacs got to new glucagon candidates. She focused on Lilly’s nasal glucagon and Xeris’ liquid-stable glucagon autoinjector, both of which have been submitted to FDA (decisions expected ~2Q19-3Q19), and we note that Zealand also has a liquid-stable phase 3 candidate in development. Dr. Isaacs anecdotally highlighted the need for more patient-friendly glucagon administration options, relaying the story of a patient who has passed out from hypoglycemia: His wife told her that she would rather call an ambulance and wait than try to use one of the currently-existing glucagon reconstitution kits. The audience groaned at this, giving us the sense that this hesitation around cumbersome reconstitution kits is not at all uncommon, but they also seemed genuinely excited about both of these coming products. Dr. Isaacs also highlighted that nasal glucagon has been shown to be just as effective is patients with nasal congestion and explained that no inhalation is needed – the patient truly doesn’t have to do anything.

• Drug Devices: Dr. Isaacs was animatedly excited about Bydureon BCise, the new autoinjector for AZ’s once-weekly GLP-1 that launched in the US in 1Q18 and recently received a positive CHMP opinion in the EU. She recounted how, when Bydureon hit the market in 2010 as the first once-weekly GLP-1, her excitement was severely tempered by the complicated reconstitution tray procedure required of patients. Even the Bydureon pen had significant shortcomings, given the 80 taps required to mix the medication and the larger needle patients had to attach. In contrast, the BCise autoinjector requires only 15 seconds of shaking and, while the needle isn’t any smaller (the once-weekly formulation inherently necessitates a longer needle), patients don’t have to see it. So far, AZ management has been quite positive about the BCise launch, and it seems like the device is starting to attract more patients. We’ve heard relatively more about needle gauge at this meeting than others; on Saturday, Ms. Lucia Novak highlighted in an Ozempic product theater that the product’s pen uses a very small 32 gauge, 4 mm needle, smaller than any other once-weekly GLP-1 agonist – this is on par with a typical insulin pen needle and is equivalent to those used with Victoza; Trulicity’s autoinjector uses a slightly bigger 29 gauge, 5 mm needle. The Bydureon pen uses a 23 gauge, 5/16’ needle.

• Insulin: Dr. Bzowyckyj dedicated a significant amount of time to explaining and contextualizing biosimilar insulins, detailing how the biosimilar approval process is more rigorous than for generic, small molecule therapies and more closely resembles the NDA approval process. He assured the audience that biosimilar products are functionally equivalent to their originator product in terms of both PK and PD profiles. And while biologics aren’t as easy to make as generics, they should still help drive down costs: Basaglar (biosimilar insulin glargine) is currently priced at a ~15% discount (median average wholesale price of $253/1,000 units) to other basal insulin products ($298/1,000 units for Lantus, $323 for Levemir, and $355 for Tresiba). Dr. Bzowyckyi speculated that, once Merck’s Lusduna Nexvue (tentatively FDA approved, pending resolution of patent litigation from Sanofi) hits the market, costs could be driven down even further and potentially even more on par with the 30-40% reduction observed with typical generic market entry.

3. Ms. Patricia Garnica Makes a Strong Case for Premix Insulin, Especially as an Alternative to Basal-Bolus Regimens; Points to Nuances Between Basal and Rapid-Acting Insulin Analogs

In a marathon session on choosing insulin for individual characteristics, Ms. Patricia Garnica gave a pro/con rundown of current insulin options, highlighting the use of premix insulin to minimize injection burden and illuminating key differences between existing basal and prandial analogs. For context, she outlined how regular insulin and NPH, which are both recombinant insulins but created slightly differently (NPH lasts longer and peaks less), were really the only options until nearly the year 2000 when insulin analogs hit the market. Despite the fact that all analogs are designed to mimic normal physiology, however, Ms. Garnica asserted that no two insulins are truly the same (see below): For example, Sanofi’s Lantus and Novo Nordisk’s Levemir both take ~one to two hours to start working, but Lantus has a more stable action profile over time. Levemir’s action drops off more rapidly than Lantus’, around 14-16 hours, so it’s more important to dose Levemir BID than Lantus. She emphasized that this has important practical implications: If a patient is experiencing hyperglycemia right around the time of their next Levemir dose, this property of the insulin is likely to blame. But, she says, it can also be an advantage: In patients with renal disease, Ms. Garnica prefers Levemir over Lantus because it’s more easily cleared from the system, and you don’t want a lot of residual insulin action. Moreover, rapid-acting insulins, typically thought of as interchangeable (especially by payers and PBMs), actually have important nuances in their pharmacokinetics. While their PD profiles are the same, the way they peak and are absorbed and metabolized are a bit different (e.g. insulin aspart is a bit faster and sharper, while insulin lispro rises slightly more gently). The advent of insulin analogs, she further explained, also gave rise to better premix insulin options, which carry both basal and prandial action. There are currently five premix options: (i) Novolin 70/30 [NPH/regular], (ii) Humulin 70/30 [NPH/regular], (iii) NovoLog 70/3 [NPH/aspart], (iv) Humalog 75/25 [NPH/lispro], and (v) Humalog 50/50 [NPH/lispro]. While premix insulin is inherently limiting in that the components cannot be adjusted independently, it is significantly more affordable for patients, especially those who do not have insurance (Humulin 70/30 runs ~$15/vial). Ms. Garnica also explained that premix can be a great option for patients who would be considered ready for basal-bolus therapy but aren’t ready to take on such an intensive regimen. Basal-bolus represents at least four injections/day (five if basal insulin is split and even more if patients are on high doses), but NPH can give both basal and bolus insulin action with only two injections before breakfast and dinner. In weighing these options, it’s critical to listen to what the patient wants and thinks they can do: “It’s better to give someone premix insulin than a basal-bolus regimen they won’t do.” We strongly agree with this perspective, and we’re also reminded that patients sometimes don’t have a much of a choice what insulin they take in the first place – and many don’t want to take it at all due to so much stigma attached (many also do not know that many formulations are easy to take). NPH and premix insulins can be decent options for some patients, particularly those not at any risk of hypoglycemia; ideally, no patient would be forced to take these due to cost, when they might prefer, for example, a next-gen basal insulin, but this is an incredibly naïve view in the US. In the end, Ms. Garnica also came down on the issue of cost, “I have to give my patient whatever insulin the insurance covers, and that’s not fair. I’m unable to help my patients help themselves.” We would disagree about how “fair” it is – this is the healthcare system in the US and if HCPs and patients do not agree with it, they should look to unite and advocate together. Single voices protesting will not move the dial in our view, sympathetic though we are to Ms. Garnica’s views.

• Ms. Garnica observed that many HCPs simply don’t understand the differences between regular insulin, NPH, and premix insulin. For example, “Novolin” is often written down, and Ms. Garnica has to call to figure out whether the HCP means Novolin N (for NPH), Novolin R (for human recombinant), or Novolin 70/30, which has huge implications for how patients use each insulin. We have heard that the practical knowledge of how to use human, NPH, and premix is being lost on younger physicians as newer insulin formulations become more dominantly used, and it is concerning that this could result in sub-optimal care and even danger to many patients. Perhaps above all, Ms. Garnica emphasized that adjustments with premix insulin can be difficult, patients absolutely need to eat three meals/day, and injections have to be given before meals. These restrictions and instructions have an enormous impact on the efficacy and safety of these insulins, so it’s critical that providers understand and properly communicate them to patients.

4. Personalization is Key: Dr. Eran Segal Talks Individual Responses to Diet and the Impact of Gut Microbiota, Illuminating Opportunities for Precision Medicine in Nutrition

In a captivating talk to a beyond-full room, Dr. Eran Segal of the Weizmann Institute of Science presented evidence that gut microbiota composition drives personalized blood glucose responses, provoking a fair share of ooh-ing and aah-ing from the audience. Dr. Segal is using his background in computer science and mathematics to lead a group taking a highly data-driven approach to nutrition, and he presented data from The Personalized Nutrition Project, which aims to ascertain how different people have different postprandial responses to the same foods. In this study (n=800, without diabetes or prediabetes), participants were administered standardized meals and then tracked by CGM in order to determine blood glucose responses. Although each individual participant demonstrated consistent responses to identical meals across different days, responses to the same meals across participants varied widely (see figure below). Dr. Segal argued that this data suggests any single, prescriptive diet will have limited efficacy in a large population, at least as far as balancing glucose levels goes, as any given person can display dramatically different responses to identical foods. Of course, the question that naturally follows is, what determines this variability? Is it a function of overall metabolic health (insulin sensitivity, beta cell health, etc.)? In fact, between-persons variability is associated with many different factors, but the most novel association identified by Segal’s group was with gut bacteria composition and the metabolic pathways represented by these bacteria. Dr. Segal’s group then applied these findings in a smaller pilot study, constructing a predictive algorithm incorporating baseline gut microbiota and other factors to personally tailor diets to individual characteristics. In testing personalized “bad” and “good” diets, Dr. Segal’s group found that the algorithm-based diets can reduce postprandial spikes and lead to glucose profiles with dramatically improved time-in-range (see graph below), albeit in a small sample (n=26). Importantly, participants in these studies were not patients with diabetes, and we would love to see Dr. Segal’s group do similar studies with this high-need patient population. Excitingly, it appears that his group currently has studies underway for individuals with prediabetes (!) and gestational diabetes as well. We were also intrigued at the level of interest the AADE crowd expressed in the microbiome: In our sense, this area of research – while very promising and interesting – is still relatively far away from offering practical recommendations for patient care, which AADE talks tend to focus on. Given how hotly-debated nutrition continues to be, we’re eager for more science that can help people better figure out what, how, and when to eat and excited about the down-the-line applications of this research. It’s clear from this session that diabetes educators see a deep unmet need in nutrition. We were also excited to learn that the application of this exciting research may not be as far off in the future as one might expect. Commercially, Dr. Segal’s algorithmic approach has already been incorporated into the DayTwo app, which is now available on US markets and provides personalized diet recommendations to users based off customers’ microbiome samples. We can’t wait to try this out, though are slightly skeptical of the message reps sent us that it alleviates the need for people to wear CGM. In the app’s list of “Avoid” items we saw in the exhibit hall, basically all of them were synonym for sugar – how individualized does this really get?

• Although not discussed in this talk, Segal’s group also recently published a paper in Nature demonstrating that environment is more important than genetics in determining gut microbiota composition. The study examined genotype and microbiome data for >1,000 individuals and found that the gut microbiome is not significantly associated with genetic ancestry. Conversely, similarities in gut bacteria are seen between individuals who share a household and have other similarities in terms of diet, drug use, and anthropometric measurements. These findings reflect the importance of addressing social determinants of health and understanding the environmental context of health, which can have important consequences for metabolic function and dysfunction separate from genetics.

Big Picture Highlights

1. Dr. Fradkin and Co. Overview NIH-Funded Diabetes Studies: AID, GRADE, T2D in Youth, T1D Treatment/Prevention, DCCT/EDIC, DPP/DPPOS

NIDDK’s Dr. Judith Fradkin presided over a phenomenal session, where she and two renowned CDE study coordinators provided the status of and commentary on ongoing/future studies and the “greatest hits” (DCCT/EDIC, DPP/DPPOS). Dr. Fradkin’s overview touched on NIH’s AID and decision support funding, HiRN (Human islet Research Network), type 1 prevention (TEDDY, TrialNet), type 2 diabetes in youth (TODAY, RISE), and gestational diabetes (HAPO). UCSD’s Ms. Gayle Lorenzi spoke about DCCT/EDIC (she’s been with the study for 30+ years and counting!) and MGH’s Ms. Mary Larkin expounded upon the DPP/DPPOS and GRADE. Notably, according to Dr. Fradkin, there may be a plan to conduct a side study with SGLT-2 inhibitors to “benchmark” them against those in GRADE.

• Ms. Larkin reminded attendees that the GRADE study (directly comparing effectiveness of SUs, DPP-4s, GLP-1s, and basal insulin) is in the follow-up phase, with findings expected to be released in 2021. The primary outcome is time to A1c of 7%+, and sub-studies include investigation of microbiome, relationship between A1c and glucose (using CGM), emotional distress, and cost across the four treatments. When pressed in Q&A why SGLT-2s weren’t included in the study design, Dr. Fradkin responded: “Just based on the budget for GRADE, we only had power to compare four drugs When we go from four to five, the number of comparisons goes up astronomically, and the number of participants goes up substantially. We had been burned with the DPP in the past; when it started, there was a fourth arm, troglitazone. At that time, it was not yet an approved drug, and it turned out to have some substantial hepatic toxicity, so it was dropped. In GRADE, SGLT-2 inhibitors were not approved for type 2 diabetes at the time, and NIDDK was leery about again using an unapproved drug. We also wanted to use drugs that had substantial market share and were commonly used. Obviously, in retrospect we would’ve’ loved to include an SGLT-2 inhibitor, and we’re talking to NHLBI and PCORI about studies that might be done say to compare SGLT-2 with GRADE-like design, maybe compare it to one of GRADE interventions to benchmark it a bit. So far, that type of study hasn’t materialized.”

• Dr. Fradkin displayed a slide with updates for the four NIH-funded AID trials before proceeding to strongly endorse efforts to enable AID device interoperability. Three of the trial timelines were as expected, based on the last update at ATTD: We were glad to hear that the Cambridge DAN-05 study (130 youth) is recruiting now; the DreaMed/Medtronic FLAIR study is “recruiting ~Fall 2018”; and the iDCL trial is “recruiting now” (Tandem’s Control.IQ pivotal trial is already enrolling and the Roche-Senseonics-TypeZero system’s study is expected to begin in 3Q18). Curiously, a study of Beta Bionics’ bihormonal (insulin+glucagon) system is listed as “recruiting ~mid-2018” – at Friends for Life, Dr. Ed Damiano said a pivotal trial will start in late 2019/early 2020, so we imagine Dr. Fradkin’s slide was referring to the ongoing bridging study leveraging the integrated iLet device. Dr. Fradkin was very excited about the “very novel” TypeZero InControl algorithm in particular, as it has the ability to link a variety of sensors and pumps, which could give the patient a lot more choice (the study’s numerous protocols use devices from Roche, Tandem, Insulet, Dexcom, and Senseonics). Pointing to the “sobering” T1D Exchange data showing that the mean A1c for teens is ~9% (the pre-DCCT standard of care), she said, “The whole issue with technology for type 1 diabetes is whether they will use it.” Well said! She also touted NIH’s support of the search for additional signal inputs for closed loop (e.g., heart rate, physical activity) and open loop decision support (displaying UVA’s CGM-based MDI dosing support system).

  • Dr. Fradkin pointed out that the $2.8 billion allotted for the type 1 diabetes Special Diabetes Program over the past two decades has touched essentially every novel diabetes technology on the market: MiniMed 670G, FreeStyle Libre, Xeris’ glucagon rescue pen, Dexcom G6 iCGM, Senseonics Eversense. Thank goodness JDRF and other instrumental advocates were successful in persuading congress to renew the program for another two years – it was touch-and-go for a while!

• Dr. Fradkin positioned the rise of type 2 diabetes in youth as “one of the most vexing problems we face today…sad to say, we really do not have an effective way of treating type 2 diabetes in children.” SEARCH showed that type 2 is on the rise in youth (especially in some minority populations, where a child with diabetes may be more likely to have type 2 diabetes than type 1). The TODAY (metformin vs. metformin vs. rosiglitazone vs. metformin + intensive lifestyle intervention) and RISE (glargine for three months followed by metformin for nine months vs. metformin for 12 months vs. metformin+liraglutide) studies found none of the interventions to be effective in preserving beta cell function, presenting “one of the most pressing conundrums we need to address.” When asked in Q&A, she reiterated that this problem is a “really tough nut to crack,” since approaches that have proven effective in adults (metformin, lifestyle interventions) have fallen flat in pediatrics. The current plan is to gather thought leaders and try to come up with new strategies. “But we have to do something,” she concluded, “it’s too important a problem to just give up.”

• Other NIDDK-funded type 2 diabetes study updates: (i) The D2d study of vitamin D in prediabetes will read out in early 2019. Each participant was followed for incident diabetes for three years – the period has come to an end, and patients are currently receiving the final assessments for type 2 diabetes; (ii) Full results from the RISE study in adults will be available in early-to-mid-2019.

• One answer to accelerating prevalence of type 2 diabetes in youth is to more effectively understand and address maternal hyperglycemia. The HAPO study found that ~18% of US pregnancies are tainted by hyperglycemia (using strict HAPO criteria). Hyperglycemia during pregnancy carried a 7x increased risk of type 2 diabetes in mothers (about half of women with gestational diabetes will develop type 2 diabetes within 5-10 years of giving birth), and GDM confers a 1.7x increase in childhood obesity risk to offspring. The next steps, according to Dr. Fradkin, are to use CGM to understand: (i) when in the course of pregnancy glucose levels become elevated; (ii) whether earlier diagnosis and treatment would prevent metabolic sequela in mother and offspring; and (iii) the best treatment options.

• Ms. Lorenzi reiterated that the EDIC trial is going strong, and was renewed in 2017 to continue out to 2022 (bringing the total trial length to 28 years). We are looking forward to seeing results from the future initiatives, including hearing impairment in type 1, the relationship between hypoglycemia and cardiac arrhythmia (individuals were monitored for 14 days, presumably with CGM and a Holter monitor), skeletal (bone) health, and neuroimaging (marrying the cognitive information collected throughout EDIC with functional brain changes). When will EDIC come to an end? “It’s up in the air and anybody’s guess. There’s always more to be learned.” Yes!

• Ms. Larkin shared future aims for the 3^rd phase of follow up for the DPP outcomes study (DPPOS-3): (i) Examine the long-term effects of metformin on CVD and cancer (metformin not approved for prediabetes, but this cohort is the largest randomized exposure to metformin and could suggest some benefit; cancer data will be out in the “next couple years” and CV will not be available for another eight years); (ii) Look at the long-term effects of DPP intervention on microvascular outcomes, glycemia and diabetes development, and outcomes sensitive to joint effects of dysglycemia and aging, quality of life, and cost; and (iii) the clinical course of dysglycemia over the continuum from prediabetes through early biochemical diabetes diagnosis to clinically-relevant complications.

• Dr. Fradkin didn’t have specific updates on HiRN, but touted efforts in implantation of human iPS-derived cells, re-programming/transdifferentiating other cell types, and beta cell replication. She noted that some of the preclinical NIH-funded iPS work has been tested through industry partners, who are now testing in people. This was presumably a reference to ViaCyte, which is currently running a phase 1/2 trial of its second-gen islet cell replacement therapy (study completion expected in December 2020).

• TEDDY – which aims to identify the environmental trigger of type 1 diabetes – is expected to complete in 2023, and is “collecting every biological sample possible.” To date, investigators have collected nearly three million samples. The first 114 to develop type 1 diabetes and the first 419 with autoantibodies have been tapped to be further evaluated in a nested case-control study. Meanwhile, Dr. Fradkin explained that TrialNet is running intervention trials at every stage of type 1 diabetes, and trying to screen 20,000 relatives of type 1s every year (currently hitting ~15,000). She urged educators in the room to refer family members of patients to the study, emphasizing how easy it is to enroll.

• The stated purpose of the 1.5-hour session was to inspire attending educators to work in clinical research. All of the speakers spoke to the important role of the CDE (“critical to the success of studies”, per Ms. Larkin) and how rewarding the career is, particularly as they form such strong bonds with study participants.

2. NDPP Enrollment Up to Nearly 235,000; >2.5 Million Prediabetes Ad Campaign Video Views; $104 Billion Annual Medicare Diabetes Spend; Letters to Verma/Boehler Go a Long Way on Virtual DPP Reimbursement

CDC’s Dr. Ann Albright shared that the number of National DPP enrollees has grown to nearly 235,000, up ~15,000 from June and triple the 75,000 in January! Additionally, she noted that there has been a steeper rise in enrollment. We wonder to what extent this sizable uptick is tied to increasing viewership of the CDC/ADA/AMA/Ad Council’s prediabetes awareness campaign videos, which have now accrued views from >2.5 million people (“breaking all records”). Phase three of the awareness videos – “another really fun, attention-grabbing campaign” – is set to go live on World Diabetes Day on November 14^th. CMMI Deputy Director Ms. Nina Brow-Ashford, who was instrumental in securing Medicare reimbursement for the DPP, explained why it was a no-brainer decision: 25% of Americans 65+ years of age are living with type 2 diabetes, and care for them costs Medicare $104 billion annually (and growing!). Asked during Q&A, Ms. Brown-Ashford had nothing new to report on Medicare reimbursement for virtual DPP, suggesting that any virtual reimbursement model would come out of CMMI, and that letters to CMS Administrator Dr. Seema Verma and CMMI Director Mr. Adam Boehler “go a long way.”

• “It’s imperative that we do not grow faint of heart. What will people say when they look back at us? Did we stand up? Did we meet the challenge? Because we are being overtaken by diabetes.” – Dr. Albright

• “It’s virtual now, which is incredibly important for scale and for people who want prevention delivered that way.” – Dr. Albright

• “Our whole mode has to be problem solving. Let’s problem solve let’s join forces, because we cannot allow the current trajectory we’re on to continue.” – Dr. Albright

3. Dr. Robert Gabbay Outlines the Growing Importance of Diabetes Educators as the US Shifts Toward Value-Based Healthcare, Advocates for Risk Stratification

In a phenomenal keynote address on Friday morning, Joslin’s Dr. Robert Gabbay offered the audience a primer on the ongoing shift toward value-based healthcare, positioning diabetes educators as the catalysts of change in diabetes. Dr. Gabbay gave a similar, incredibly well-received talk at AADE 2017, so we weren’t surprised to see him deliver this opening keynote – many commented last year that his presentation should have been a keynote! President Ms. Donna Ryan’s address on patient-centered earlier in the morning offered the perfect segue into Dr. Gabbay’s. As he explained, the 2015 passage and ongoing execution of the Medicare Access and CHIP Reauthorization Act (MACRA) has already fundamentally changed how Medicare reimburses HCPs, shifting payment away from a “fee-for-service” model that promotes volume to a “value-based” model that prioritizes quality of care and efficient resource utilization. Dr. Gabbay described how many seemingly non-sensical processes and motivations in healthcare can be explained by the principle of money and detailed how this new legislation aims to incentivize practices that actually lead to better quality of care (and likely lower long-term costs). Specifically, doctors are now evaluated by Medicare on four components: quality of care, resource utilization (i.e. cost of care), engagement activities with patients, and skilled use of electronic health records; importantly, quality of care will be highly weighted compared to other components. In explaining how this shift relates to diabetes care, Dr. Gabbay outlined how diabetes care is traditionally a “cost center” in fee-for-service healthcare systems because the goal is to prevent complications rather than perform procedures and because the financial incentives for these actions are not high; downstream, surgical centers are revenue centers that help hospitals reach their bottom lines, as procedures are more highly reimbursed by payers. This status quo will be turned upside down as the expected shift toward value-based care takes hold across public, and then private, payers. Most importantly for this audience, Dr. Gabbay underscored that diabetes educators can be the “folks that save money for the healthcare system” by preventing complications. These preventative measures – already so critical – will only hold greater importance in a value-based system, given they are relatively inexpensive compared to, for example, cardiovascular events or hospitalizations for hypoglycemia. Moreover, we would add that the cost of diabetes care continues to increase nationally, and diabetes educators have a key role to play in helping to minimize the impact of the disease on both patient lives and the healthcare system. Dr. Gabbay envisioned a new role for diabetes specialists in this changing environ, urging the audience to focus on practice coaching, care management, and augmenting digital care. Further, he especially highlighted the importance of risk stratification within care management, noting that five percent of patients (the “highest risk” group) are responsible for half of all health care expenditures in the US, overall. Stratifying patients based on individual risk (for example, he proposed, patients could be classified into potential categories of risk: poorly controlled with complications, high A1c, newly diagnosed or A1c within one point of goal, and well-controlled) could help to improve resource utilization and provide more value to patients. Although these classifications may, at least on the surface, be a bit antithetical to personalized, patient-centered care, we do recognize the potential value of approaching medicine this way – though we also think the field needs to be wary of this practice coming at the expense of other patients.

4. Predictors of Diabetes Education Program Attendance: Age, Copay, Socioeconomic Status, A1c, # of Diabetes Meds, Metformin, and Insulin

University of Missouri-Kansas City’s Dr. Andrew Bzowyckyj presented results from his analysis of EMR data to identify predictors of non-attendance to a diabetes education program (“DSMES”). He was particularly interested in evaluating the role of social determinants, hypothesizing that factors such as socioeconomic status, neighborhood and physical environment, healthcare access, employment, and education might be linked to attendance. Although the specific DSMES program spanned three classes plus a three-month follow-up, for the purpose of this study, Dr. Bzowyckyj classified attendance as participating in just the first class…a low bar for engagement, but a start. The following factors were found to be significant predictors:

(i) Age – Dr. Bzowyckyj noted “a very clear linear pattern,” in which each additional year increased the likelihood of attendance by 2%;

(ii) Required copay – not surprisingly, those for whom a copay was required were 38% less likely to attend;

(iii) Socioeconomic status – patients on Medicaid or those receiving a Truman Medical Center discount were 31% less likely to attend than those on Medicare or with commercial insurance;

(iv) A1c – each 1% increase in A1c decreased likelihood of attendance by 4.3%, and those with A1c >8.5% were 22% less likely to attend than those with A1c <8.5%;

(v) Number of diabetes medications – while being prescribed a diabetes medication was not found to be a significant predictor, each additional diabetes medication decreased likelihood of attendance by 13%;

(vi) Metformin – patients prescribed metformin were 36% more likely to attend; and

(vii) Insulin – patients prescribed insulin were less likely to attend, but once a bolus insulin prescription was added, likelihood of attendance increased; interestingly, as the total daily dose of insulin rose, the likelihood of attendance declined.

It’s difficult to identify any clear pattern. While in some cases, it seems that the more intense the therapy, the less likely patients are to attend the session (perhaps indicative of a defeatist attitude) other findings reflect the complete opposite. While Dr. Bzowyckyj refrained from drawing any firm conclusions from the analysis, we could see how, if validated further, these predictors might be leveraged for targeted intervention. For example, participants predicted to not attend DSMES could be called upon prior to the first class to increase likelihood of participation; or, better yet, programs tailored to address the specific obstacles faced by these patient subgroups might be designed. The entire exercise sounded similar to the Helmsley-funded Cyft/Joslin collaboration, which seeks to predict which type 1s are likely to cancel appointments within 72 hours (a costly and not uncommon occurrence), and then intervene to prevent cancellation. 

5. Recruitment and Retention Strategies for DPPs: “Session Zero” Before Initiation Provides Context and Comfort to Patients; Targeting Advertisements to At-Risk Populations – Don’t Forget the Newspaper Ad

A pair of diabetes educators currently running DPPs, Ms. Erica Moore and Ms. Susan De Abate, gave insights into recruitment and retainment for DPPs – two of the greatest current barriers to uptake of the DPP, as it stands. Nearly all of Ms. Moore’s 20-minute talk was dedicated to the value of a “session zero,” or an informational session prior to the official start of the DPP. Through this, potential participants have a chance to become familiar with the space in which the in-person DPP will take place and gain a sense of what will be expected over the 12-month program, which helps ensure that they do not drop out after being caught off-guard by the commitment required. Ms. De Abate’s talk, by comparison, offered a thorough crash-course on how to start a DPP. Most interesting to us was that, with respect to recruitment, she emphasized the importance of tailoring advertisements to the target audience by having providers refer at-risk patients and including ads in newspapers and other mediums that are frequently read by the 65+ at-risk population. In her assessment, patients are more compelled to initiate and stay in the program if they have received something from a physician, so building those relationships is critical to both the program’s and the patients’ success. In an ideal world, according to both speakers, patients with prediabetes could be pulled from EMR and automatically recommended for the program – we find it painful how many barriers there are to enrollment in these programs, though we aren’t experts in the policies and regulations in the way. For context, enrollment in DPPs is an ongoing saga: Later on at the meeting, we heard from CDC’s Dr. Ann Albright, who updated current enrollment in the national DPP to 235,000 – over double the number from one year ago. While this growth demonstrates some progress and is certainly encouraging, we note that roughly 88% of the ~84 million people with prediabetes in the US are unaware of this status, meaning that the vast majority of those who could benefit from DPPs are not only not enrolled – and don’t even know that they can or should be. That said, we’re excited to see how this program will scale up over the next decade and the impact that digital DPPs can have. What will move the dial should be decided upon – 250,000 is a very impressive number for anything in diabetes but given the denominator, we’d love to see the CDC garner lots more funding.

• Ms. De Abate briefly touched on technology, stating that a digital DPP is “always an opportunity” for HCPs starting a new program but can be put on the back burner and addressed when one is ready to expand. We certainly understand that establishing a DPP is an intimidating endeavor in and of itself, but we would love to see greater emphasis placed on the potential of digital programs. Just last month at WCPD 2018 we heard Dr. Albright extoll digital programs as the key to scalability, saying, “We must absolutely use tech … We will never get to scale of anything unless we use digital.” Technology enables scale, allowing those who can’t or won’t travel to a site to participate in a DPP. On the other hand, Ms. De Abate’s reminder that the majority of those who can benefit from DPPs are over the age of 65 is an important consideration for technology-based programs. Additionally, we note that CMS reimbursement for digital DPP programs remains limited to make-up classes and rural patients for now, and to our understanding this isn’t slated to change anytime soon, which is unfortunate in our view since the needs are so high.

• According to Ms. De Abate, once the CDC accepts an application for DPP recognition, the program will be expected to begin submitting data from that day forward. As such, thorough preparation on the back-end of the program before a CDC application is submitted should be done to ensure organization and support.

6. Language’s Dynamic Duo: Drs. Jane Dickinson and Susan Guzman Elaborate on AADE/ADA Joint Recommendations for Talking About Diabetes: No More “Diabetic” or “Control”

In an interactive session, powerhouse duo Dr. Susan Guzman and 2019’s Diabetes Educator of the Year Dr. Jane Dickinson guided attendees through the 2017 AADE/ADA recommendations for diabetes language; Dr. Guzman and Dr. Dickinson were lead authors of the paper. Through role-playing examples, the presenters guided the audience through the paper’s evidence-based recommendations and examples of implementation. Since the publication of this paper, we’ve seen the person-first, non-stigmatizing language movement in diabetes and obesity gain significant momentum. While this much-needed linguistic revolution has been building since at least 2012 (when Diabetes Australia put forth a similar paper), the recommendations suggested by Drs. Dickinson and Guzman have been key in moving the needle towards progress in reducing stigma and negativity around diabetes. Find our original coverage of the paper here, and our interview with Dr. Dickinson here; included here are some of the most powerful quotes from the session:

• “50% of people with diabetes do not like the word diabetic. If it bothers 50% of people, we should stop using it.” - Dr. Dickinson. By labelling someone “diabetic,” she explained, their identity and disease become inseparable – a negative and even disparaging association. The principle is known as “person-first” language, and we note that it also applies to obesity – saying “he is obese” is prescriptive and carries the same negative connotations. An audience member provided humorous context to this concept, noting that, “we wouldn’t call someone a hemorrhoidic if their hemorrhoids were acting up.”

• “It is my hope that – until we have a cure, of course – we will lead by example and not use the harmful word, diabetic.” - Dr. Dickinson. In our view, the prospect of finding a “cure” for either type 1 or type 2 diabetes remains an uncertainty (and different people certainly define “cure” very disparately), but we love the optimism embedded in this quote. In the meantime, all stakeholders in diabetes can all be leaders in inspiring confidence and positivity through compassionate, goal-oriented language.

• “As educators, we can’t use the words ‘get them to’ when we’re talking about patients. We educate, we help, we listen, but we don’t ‘get’ people to do anything.” - Dr. Guzman. She later elaborated on this concept, stating that “get them to” puts the HCP and their agenda before the goals and needs of the patient, which should always come first. It’s also important to realize that patients are the ones putting in the work in diabetes: Between three-month appointments, the onus is completely on the individual to manage their diabetes, day in and day out.

• “Control is perhaps the most harmful word in diabetes today.” - Dr. Dickinson. This term sets the unrealistic expectation that diabetes can always be managed, implying failure when patients do not reach the targets put forth by HCPs. The next step, Dr. Dickinson says, is removing the word “uncontrollable” from ICD10 codes.

• “Strength-based language acknowledges efforts, not just outcomes.” - Dr. Guzman. For example, family, friends, HCPs, and educators can say, “thank you for filling out your diet log,” or “thank you for coming to your appointment,” even if the patient’s outcomes do not reflect the work they are doing. This goes hand-in-hand with not shaming patients for what they haven’t done.

• “It turns out, you can teach people empathy by helping someone take other peoples’ perspectives.” - Dr. Dickinson. To emphasize this point, Drs. Guzman and Dickinson displayed a patient profile with and without psychosocial information. When the details were present – a stressful family situation and high PHQ-9 score (an depression assessment) – the patient’s lab values were brought into an entirely new light. 

• “People with diabetes are too often thinking of themselves as a collection of numbers – a collection of numbers that is not quite good enough.” - Dr. Dickinson.

• “Imagine a body part that you’re not particularly proud of. Now imagine that you are going into the doctor’s office to have that body part not only examined, but critiqued. That’s how people with diabetes can feel.” - Dr. Guzman.

7. New JDRF Video Series on Pregnancy and Type 1; CGM Recommended for All Type 1 Women During Pregnancy

A particularly emotional, tear-jerking session on type 1 diabetes and pregnancy  featured JDRF’s recently-released series of videos following one woman’s journey through pregnancy and delivery. The videos, published in June, can be found on TypeOneNation.org and JDRF’s YouTube page and are intended to highlight the unique challenges associated with pre-pregnancy planning, each trimester, and delivery/post-pregnancy. The videos mostly explored a patient’s personal fears, hopes, and experiences, which we believe will be immensely powerful in helping some women with diabetes feel less intimidated by pregnancy and like they are not alone in their trials, tribulations, and successes.

• Florida Medical Clinic’s Ms. Michele Laine, who created the videos with JDRF, explained that she “likes to push using CGM” for all her type 1 patients during pregnancy. She “almost makes CGM mandatory” provided it is affordable. Yes! She emphasized that CGM has been a “lifesaver,” as have pumps. For patients who may be reluctant to initiate CGM, JDRF’s Dr. Nicole Johnson suggested sharing results from CONCEPTT finding CGM to be linked with better neonatal outcomes; “That’s such a compelling argument for moms-to-be.” (And we believe this study underestimated the treatment benefit, since it used such an old CGM.) She also highlighted the importance of careful language during these discussions, reminding attendees to avoid ultimatums and to focus instead on collaborative discourse.

• Both Ms. Laine and Dr. Johnson noted that post-delivery can be particularly challenging for women, as patients’ insulin needs are dramatically reduced and hypoglycemia is common with breastfeeding. Dr. Johnson shared that the best piece of advice she received during her own pregnancy was to buy an upholstered rocking chair for breastfeeding as opposed to a wooden chair – she was told that she would be “low every day” during breastfeeding and in the event of an emergency, the baby should have a soft landing.

8. AADE President Ms. Donna Ryan Shares Her Journey to Patient-Centered Diabetes Care, Urges Diabetes Educators to be Champions of Quality, Safety, and Compassion

AADE President Ms. Donna Ryan kicked off the 2018 meeting with an impassioned, personal talk recounting her own journey into diabetes care and urging the audience to “be a voice for quality, safety, and compassion.” Invoking the spirit of the War of 1812 and the piece of US history that was made just outside Baltimore when Francis Scott Key wrote what became the lyrics of the “Star Spangled Banner,” Donna Ryan called on the room to “wage a war” on diabetes and fight to ensure that the right to access, quality, and safety is realized for all patients with diabetes. To underscore the necessity of empathetic, patient-centered care that recognizes the diversity of patient experiences, Ms. Ryan described her own unique path through diabetes care, starting with a nutrition degree from the University of Alabama and moving through work as a dietician in LA, learning Spanish to better communicate with her patients, pursuing a public health degree, going to nursing school, and then getting involved with AADE. Ms. Ryan structured her talk around several short stories of patient interactions; one particularly striking episode was centered on a young, Spanish-speaking pregnant woman with gestational diabetes who visited the hospital during Ms. Ryan’s early days in LA. Ms. Ryan described how the patient remained quiet as she explained dietary information via a translator, running through informational packets about her condition and next steps to be taken. At the end of the session, the patient asked, through her translator, where the morgue was; her 16-year-old son had been killed the night before. Ms. Ryan pinpointed this interaction as dramatically shifting her view of patient care, explaining that truly caring for patients is about “not just what we feel they need to know, but acknowledging what they are feeling right now in that moment.” For that reason, Ms. Ryan now begins every one of her patient visits with the question: “what’s important to you right now; what do you need?” We firmly agree that it is so essential to understand the other parts of a patient’s life and to work within their realities. Calling upon this experience and other similar stories she shared during this opening address, Ms. Ryan urged the audience to become leaders who lift patients up and empower them.

• The call to this type of patient-centered care was echoed later in the day, during a “Listen and Learn” session featuring a panel of local diabetes advocates and HCPs with diabetes. Ms. Shelby Kinnaird, who runs diabetes support groups and DiabeticFoodie.com, offered three cautionary tales to illustrate why many patients don’t go back to their diabetes educators. One woman, Wendy, with type 2 diabetes had lost her husband, experienced an MI and fractured arm, and then a collapsed lung after surgery. After working eight hours a day and carrying her oxygen tank to the car, she was too tired to grocery shop and cook so she would eat drive-through food. Wendy’s DE told her fast food is bad for her and she should cook; instead, Ms. Kinnaird said, she should have helped Wendy find healthier fast food options. Sylvia, a legally blind patient, was eating a ketogenic diet because she lived with her son and daughter-in-law, who ate that way; she lost weight and had better glucose control, but her DE told her a ketogenic diet was bad. Instead, Ms. Kinnaird argued, a better option would have been to explain why that diet might not be ideal and suggest healthy but non-ketogenic snacks she could keep for herself. Finally, Corey stopped taking his diabetes medications when he ran into financial trouble and soon had a heart attack and went into renal failure. A friend started taking care of him, including by cooking his meals. When they went to an educator together, they were only told that the diet was wrong, rather than learning why certain nutrients – like potassium – need to be watched carefully when one has renal problems. None of these people returned to their DE’s; as Dr. Nicole Bereolos explained at the beginning of this session, all HCPs need to focus on addressing the patient’s concerns and goals for a visit. This doesn’t mean what the provider thinks is in the patient’s best interest, but what the patient actually wants and is ready to work on: If the patient smokes cigarettes but isn’t ready to try to quit, it’s a better use of time and energy to find what they are ready to work on and help the person become healthier in that way. Finally, Dr. Bereolos emphasized attitude and tone on the provider’s part, sharing that patients say they like to visit her because she smiles at them; building a supportive, positive relationship from the start is paramount.

Exhibit Hall

Diabetes Technology

Abbott

The enormous, can’t-miss Abbott booth was buzzing, with attendees flocking to see the FreeStyle Libre and FreeStyle Pro up close. After receiving FDA approval in September (real-time) and most just obtaining 14-day wear and one-hour warmup approval in July, interest in FreeStyle Libre has not waned one bit – in fact, a product theater on the device drew a massive line of attendees that wrapped around the venue several times. One Abbott representative explained that she’s been receiving several questions regarding the differences between FreeStyle Libre real-time and Pro. Clinicians unaware of the Pro have been confused by patients who have seen marketing for a two-week FreeStyle device. However, the representative believed the confusion reflects a larger issue in communicating the pros and cons of personal vs. professional CGM in general. We were also interested to see an Abbott-branded “Sugar Tour” bus featuring the work of two artists from Ireland. Several sculptures created entirely from sugar cubes were on display – the below sculpture represents the average amount of sugar consumed by an American in a year! The sculptures are intended to serve as an educational tool to drive prevention efforts, and the artist shared that they especially aim to reach those with prediabetes. We love this initiative and salute Abbott for sponsoring such a creative approach in prevention!

Ascensia

The Contour Next One’s newly upgraded paired Contour Diabetes app was heavily featured at the Ascensia booth. A representative shared that the company is “working towards” Apple Health integration, anticipating that we might hear news on this front “sooner rather than later.” Currently, manual insulin dose entry is necessary in the app, but with Apple Health now including insulin data, the hassle of data input could be avoided for those using connected pumps or pens. We’re thrilled to hear that this feature is in development. The booth also advertised the BGMs’ tethers to the diabetes tech ecosystem, highlighting the Contour Next One integration with Omnipod Dash and its inclusion in the Dexcom G5 Medicare bundle, as well as the Contour Next Link integration with Medtronic’s MiniMed 670G. Similarly, a substantial portion of the Ascensia product theater emphasized that highly-accurate BGMs will remain essential despite rising use of CGM. Although Senseonics’ Eversense, Medtronic’s Guardian Connect, and Dexcom’s G5 still require calibration, Abbott’s FreeStyle Libre and Dexcom’s G6 are zero-cal, and we expect that future CGMs will be going this way as well. With CGM popularity increasing, BGM companies will need to compete on broader fronts, especially access and innovation around strips (i.e., digital, coaching, decision support, behavior change, using BGM as a component in an outcomes-driving package, type 2s that cannot get CGM, etc.). Ascensia is taking a great digital stance by focusing on its app and connectivity – an approach we hope to see expand further! Medtronic’s upcoming Bluetooth-enabled 670G pump is set to pair with Roche’s Accu-Chek Guide Link BGM, moving off the Ascensia BGM.

BD

Along with the customary display of pen needles, the front-and-center BD booth heavily featured its free “Diabetes Personal Assistant” app, Briight, released at ADA and in its formal launch here. We spoke with BD’s Digital Diabetes Product Leader Mr. Ed Liebowitz, who shared that Briight is close to reaching 20,000 users, split evenly between iOS and Android devices. He noted a very impressive 1,000 “active users” are being added each week and they show “strong engagement” with the curriculum content. Since ADA, educational content surrounding health insurance, activity, and food choices have been added to the app. The chat bot is being continuously improved, Mr. Liebowitz explained, and will be moving towards a “skill-based approach.” Mr. Liebowitz was especially excited to show the results of the integration with Calorie King – when users ask the chat bot if they can eat a certain food, comprehensive nutritional information is immediately generated. (The app cannot recommend if the food should/should not be eaten.) We hope to see this feature eventually built out even further; for example, a user’s blood glucose and insulin on board could be analyzed to provide specific recommendations on alternative food choices and/or exercise. Not surprisingly, Mr. Liebowitz shared that educators have been “really interested” in the app, citing an unmet need for self-management tools. While still in its early days, we continue to have high hopes for Briight and look forward to seeing future iterations that expand on the current insulin injection technique focus.

Common Sensing

Common Sensing’s small corner booth was not short on updates, offering our first-ever in-person chance to hold Gocap. The Bluetooth-enabled dose capture cap compatible with Novolog pens is still on track for October, when it will join Lantus and Apidra in available offerings (all currently out of stock, however). All are under list pricing, and the company is working on securing payer coverage. Gocaps compatible with other insulins – presumably at least Lilly’s Basaglar and Humalog – will come next year. From a commercial perspective, we were pleased to learn of a new program that offers up to 200 Gocaps simply in exchange for feedback – no cost – to clinics with low access or ability to pay! While this won’t bring in any revenue, it is a very smart way for Common Sensing to help and better understand the wants and needs of users in lower socioeconomic circumstances, a segment that could become very important for growing business.  We also heard that the Gocap Beta program, which launched in January, has been restructured. Whereas the devices were initially sold at a price of $75 in the program, site visitors will now be directed to one of three landing pages, each offering Gocap at a different price point in order to gauge willingness to pay. The consumer-facing page, www.gocap.me looks really nice, but doesn’t give pricing information – users are direct to download the app from the iOS and App stores. Common Sensing has done a super job on the user interface with Gocap, and we look forward to seeing what kind of deals it does to make it commercially available in a bigger way.

• In its current form, Gocap doesn’t have the ability to differentiate between priming and injected doses – the cap measures insulin volume before and after injecting. A one or two unit prime would not be impactful for those with high daily doses, but the difference could be quite meaningful and interfere with insulin titration algorithms for a low daily dose type 1. A rep said that a future iteration (targeted by end of year) may address this issue by allowing the user to say, “I normally prime XX units,” and subsequently subtracting XX units from the detected volume change. Assuming consistent and accurate priming, this is a very clever workaround, though a poster from ADA, however, tells us that priming isn’t the most consistent diabetes behavior. This is an advantage of Companion Medical’s InPen, which can detect priming doses.

• When we passed by the booth, we happened to notice that President Mr. James White was meeting with a Medtronic scientist. Our minds automatically jumped to Medtronic’s Analyst Day announcement that it would be launching an insulin dose capture and titration product by April 2020. Medtronic certainly has a growing number of injection dose capture companies to choose from – and possibly exploring developing a device internally – but we thought this connection was worth pointing out.

Companion Medical

If you were looking for a mob at AADE, Companion’s booth was one place to look. A rep told us that the company is growing quite rapidly, having tripled in size this year, including new Director of Strategic Marketing and Sales Enablement Mr. Steve Lamar. Mr. Lamar will be an asset as Companion looks to launch InPen, having helped do so at MiniMed, Animas, and Dexcom, where he was most recently Director of Sales and Leadership Development. He was enthusiastic, summing up his view of the company’s position simply: “We’re in a really, really good place.” Part of his optimism may have stemmed from the fact that Companion has begun to dip its toes into the realm of retail pharmacies – CEO Mr. Sean Saint told us “We are in a few pharmacies as a trial. It is a nice experience for users to be able to get InPen, for example, on the day of diagnosis so we are seeing how that works.” Nice! The bulk of sales are still presumably made through mail order, though we’re elated to see retail ramping up! News of the One Drop partnership wherein every InPen will come with a free Chrome BGM just hit the wire during AADE, but the booth did have a meter to catalyze conversation.

DANA Tech Training Lab

AADE’s DANA (Diabetes Advanced Network Access) diabetes tech resource made its debut here, positioned as a “one-stop healthcare resource that helps navigate the many new technologies people with diabetes and prediabetes can use to get and stay healthy.” Proud AADE reps demoed the platform, which includes information for providers (AADE members) on pumps, CGMs, meters, wellness apps, and digital therapeutics, along with tech courses that often come with discounts for AADE members, and also occasional polls. diaTribe.org is one of the contributors of up-to-date tech news, along with other websites. The booth also played host to p-a-c-k-e-d product presentations from contributing companies. It is great to see a consolidated hub of diabetes tech information for educators, and we look forward to seeing how much investment this receives from AADE – obviously keeping tech news up to date is a big job in the increasingly fast-paced field.

Dexcom

Dexcom reprised its much smaller booth from AACE and ENDO, which was initially surprisingly hard to find – we had expected a big presence at AADE for G6. That said, it’s probably been an expensive marketing year, and we’d guess a lot is going into digital marketing to match Abbott’s push with FreeStyle Libre. The full G6 portfolio was on display in the booth – Android and iOS apps, Android and Apple smart watches, slimmer transmitter, and improved applicator. We watched from afar as one educator got a demo of the new G6 automatic applicator next to the G5 manual applicator – the delight on her face summarized our thoughts exactly. A rep confirmed what we heard on Dexcom’s 2Q18 call: the team is racing to keep up with G6 demand. Dexcom saw much higher-than-expected record sales in 2Q18, mostly driven by G5; accordingly, we expect a nice ramp in 2H18.

Fit4D

According to CEO Mr. David Weingard, Fit4D is now officially the biggest CDE employer in the country, besides pharmaceutical (and presumably diabetes tech) companies. He didn’t provide a specific number of employees, but did promise that by this time next year, his diabetes coaching company will have more educators hired than some pharma companies. Fit4D has contracts with three of the five biggest diabetes pharmaceutical companies, a medical device company (presumably referring to Glooko), and a relationship with Humana. Fit4D has also reportedly closed a funding round, though no details on size were offered. 

Fitbit

We learned that Fitbit is still in the process of incorporating Twine, the B2B2C coaching platform specializing in facilitating coaching for diabetes, hypertension, weight loss, and smoking cessation (acquired in February). Fitbit’s Mr. Brian Gilan shared that there is a “ton of work happening behind the scenes” and expects to release news on the status of the integration “in the near future.” He explained that the goal is to keep the platform “relatively device-agnostic” (i.e., users will not be limited to Fitbit trackers, a smart move in our view) and mentioned plans to establish an “ecosystem of partner devices,” alluding to connected BGMs and scales. Coaches will have “varied backgrounds” depending on a patient’s specific conditions. The platform supports text, phone, and video calls to facilitate communication between coaches and users. We’ll be interested to see how Fitbit plays in the diabetes coaching landscape and what kind of business model routes it takes. While we’re seeing more diabetes tech companies move towards comprehensive chronic disease management – Livongo, mySugr, Omada, One Drop – it remains to be seen what role Fitbit will play. Meanwhile, pressure is certainly high – Fitbit reported its seventh consecutive quarter of YOY declines in 2Q18; will the company’s subscription-based offerings be able to counterbalance Fitbit’s less-than stellar tracker device sales?

Glooko

The Glooko booth advertised the company’s FDA-cleared Mobile Dosing Insulin System (MIDS) for titrating basal insulin in type 2s, which a rep said is starting to roll out to pilot sites. As of AACE, mass commercialization is expected by the end of the year, although no further updates have been provided since. The booth representative shared that the DreaMed Advisor Pro is slated to launch in the fall, back slightly from “end of summer.”

Insulet

At an Insulet booth dedicated to the Omnipod Dash system (nearly identical to ADA’s), reps revealed the scope of the Dash Ahead limited launch program: Dash will be available to up to 35 patients per territory (five endos per territory; up to seven patients per endo) – assuming there are at least 50 territories, that’s ~1,750 patients or perhaps more. The broad US launch is still expected in early 2019, after Insulet ramps inventory and secures broader payer coverage. A rep also told us that the company hopes to hear back on Medicare Part D bids by the end of the month. On the 2Q18 call, management reiterated that Express Scripts and Magellan were already on board for Omnipod to be a covered Part D benefit, and that other payers would be publishing their formulary schedules from the end of August through October.

• A screen in the booth touted an “Argent”-conducted survey of CDEs that found Omnipod to be the easiest mode of administering insulin – easier than insulin pens and far easier than any other pump on the market (from an HCP perspective). The report also found that the Omnipod required the fewest steps – going by the user guide – for basal/bolus therapy over 72 hours. While Omnipod requires 87 steps to deliver the equivalent of six shots per day, Tandem’s t:slim (181 steps) and Medtronic’s MiniMed 630G/670G (150 steps) all required more – though all were significantly fewer than MDI’s 486 steps! (We’d be interested to see what counted as a “step,” as this sounds like quite a lot!) The data evoke three narratives: (i) Omnipod is a very usable, less demanding system; (ii) pumps alleviate burden relative to injections; and (iii) most importantly, people with diabetes must cope with a lot of steps each day!

Medtronic (Inner Circle program details)

In Medtronic’s exhibit hall booth, we got a private first look at time-in-range goals and health-related items that can be redeemed for points in Inner Circle, the novel CGM gamification and patient engagement program that launched last week. Now available for invited Guardian Connect and MiniMed 670G users, Inner Circle pulls CGM data from CareLink and gives users “points” for more time-in-range (70-180 mg/dl) – the lowest tiers are 70%+ time-in-range for 670G users and 60%+ time-in-range in Guardian Connect users. We were not allowed to take pictures and didn’t get to see the specific items or point values, but we really appreciate that Medtronic is doing something different here with CGM data, investing in its customers’ health success, laser focusing on time-in-range goals, and aligning points redemption with better health. After this brief look, we are more impressed with what we’ve seen so far! The big questions are who it will motivate and how sustainable that motivation will remain over time. Read more details below! 

• Time-in-range of 70-180 (TIR) is framed as a monthly goal within Inner Circle, with points given for reaching different benchmarks: 400 points are given for 670G users that reach 70%-79% TIR, 600 points for 80-89% TIR, and 800 points for 90%+ TIR. For Guardian Connect CGM users, the TIR goal tiers are ten-percentage points lower at each respective point level: 60-69%, 70-79%, and 80%+. Users must have at least 15 days of sensor data to get the points, encouraging consistent CGM wear and at least once-monthly CareLink upload for 670G users. As a mobile CGM, Guardian Connect data flows to CareLink – and therefore Inner Circle – automatically.

  • Medtronic used the 670G pivotal and real-world data from Guardian Connect users to frame these benchmarks. They seem very reasonable and very grounded in actual data – nice! As a reminder, 670G’s pivotal saw 72% time-in-range on average, which means a sizeable portion of the population was both above and below that level. On average, the 72% time-in-range in 670G’s pivotal delivered quite strong A1c (<7%) and hypoglycemia outcomes (<3%) on 670G, so prioritizing 70%+ TIR makes a lot of sense. Guardian Connect is aimed at MDI users, presumably reflected in the slightly lower benchmarks than hybrid closed loop. The Guardian Connect real-world data we saw at ATTD 2018 showed ~61%-62% time in range over a nine-month period in n=258 users. Over 70% TIR has been thrown around as a benchmark ever since the 670G pivotal and subsequent real-world data; conversely, we’ve heard much less benchmark discussion for MDI+CGM users.

• Points can be redeemed for “health-related items.” We didn’t get to see the specific items and associated point values, but obviously these will play a big role in how motivating the program is and the business model economics of the program. We can’t wait to learn more on this front – what will motivate people? What will improve health outcomes? What “health-related items” will Medtronic include?

• Interestingly, the point distribution within Inner Circle favors the health outcome rather than viewing an article with pump tips or watching an educational video. While the latter are available within Inner Circle (see below), these generate 25 or 50 points– a sliver compared to the 400-800 points for achieving one of the TIR goals noted above. We love this! Medtronic Chief Patient Officer Louis Dias highlighted that a lot of wellness programs focus on doing activities, while this one is focused on outcomes. It’s like value based care for patient engagement!

  • Points accumulate within Inner Circle quite visibly in the user interface, a smart gamification move. Seeing the points tally up in a very visible on-screen box should be motivating.

• How will Medtronic define a $/point value that maps to improved TIR or other health outcomes and/or a business model? For example, how much cost savings would a 10-percentage point improvement in TIR generate? Could Medtronic build a business around improving TIR from 62% to 72%? And if so, what level of point redemption is appropriate for that kind of improvement? And if can’t take this tack, simply encouraging users to upload their data obviously allows Medtronic to acquire more data, build stronger products, and bring more data to payers. Clearly there will be heaps of learning here, so for now we assume the point values/redemption items are guesses and may be conservative.

• Other questions: What is an acceptable motivating redemption level for points and items? Over what time horizon? What health-related items will be most popular? How sustainable will the engagement be over time – will this have cool factor, but then see people drop off? Will those spending low time-in-range be motivated to get much better, or will this only reinforce those already doing well?

• Over time, users will be able to set customized challenges – the more ambitious the challenge, the more points will be awarded. While this functionality is not currently available, a user could set a goal to hit a TIR of 75% within two months, up from a current level of 52%. The platform would recognize this is a big jump and award even more points accordingly.

• Inner Circle is actually a mobile-responsive website, not an app. Medtronic decided strategically not to go with an app, in part because it enabled a faster path to launch. The website approach also allows for faster iteration and A/B testing, while still facilitating an app-like experience. The vast majority of early users (number not specified) have used Inner Circle on their phones. Medtronic is also working to make it easy to add an app icon to a user’s own smartphone home screen – clicking on it would open up a web browser and go straight to the Inner Circle website.

• Inner Circle appears online as a tiled display, including the monthly time-in-range level and goal and separate tiles with articles, videos, surveys, and content. The one piece of content we saw was a “Pump Tricks” PDF. Another tile allowed users to share a tip, which Medtronic will curate and share back within a tile. There is no forum/community at this point – the approach is a one-way, highly curated platform in this first-generation. Over time, Medtronic could obviously build this out and allow users to have friends, give each other kudos (like Fitbit/Strava), etc.

mySugr

mySugr’s bright green booth was adorned with a cheeky marketing campaign for its unlimited strips bundle: “Diabetes Costs Suck.” We saw the mySugr’s Bundle’s packaging for the first time: a glossy bright green box (“made with love”) that included an Accu-Chek Guide BGM, 250 Accu-Chek Guide strips, and lancets – see below. It looks awesome and does a nice job matching the great packaging One Drop has also put together for its similar Premium. mySugr was marketing a new website – www.mysugrbundle.com – which offers the unlimited strips (auto-shipped based on usage), meter, coaching, and mySugr Pro for $39.99 per month. Reps mentioned this introductory price is likely to increase, but it will still be competitive. Though mySugr’s booth was next to Roche’s, the startup continues to do an outstanding job of maintaining its independence (cheeky marketing included!) under the BGM giant. 

One Drop

One Drop’s booth treated us to a number of updates on the diabetes mobile app, coaching, and unlimited strips program:

• One Drop still plans to launch Automated Decision Support (forward-looking glucose prediction) for people with type 2 not on insulin in Q3 2018 (i.e., by the end of next month). We first saw this cool feature at ADA in June, which gives a forward-looking glucose forecast up to 12 hours ahead based on limited fingerstick data, food logging, exercise data, and other contextual inputs (e.g., demographics, weight, A1c). The reps told us there was a buzz and lots of questions and excitement from CDEs about this addition. Many educators, according to One Drop, said non-insulin users “feel like they are flying blind and having some guidance on where they are going will be game changing.” We completely agree! Other booth attendees asked about when this feature will be available for insulin users, something One Drop is working on. This latter feature may require a regulatory path, while the type 2 non-insulin feature doesn’t (as we understand it).

• One Drop | Experts program for Gestational Diabetes will launch this coming week – we look forward to hearing more, since there are many with gestational diabetes who could benefit from mobile coaching and education. Currently, there are two Experts education programs listed on One Drop’s website: one for Advanced Carb Counting and another on Overcoming Diabetes Burnout.

• One Drop’s Revive, its Diabetes Prevention Program, is now expected to launch by the end of this year – this is 2-3 quarters behind the original goal to launch in “1Q18.” Revive received pending CDC recognition last October, and we’re excited to see another mobile DPP available for people with prediabetes.

• One Drop’s new partnership with Companion Medical, announced during AADE, also drew interest: Companion will begin shipping a free One Drop Chrome Bluetooth-enabled BGM with every eligible InPen in the US. The Companion app will pull glucose data from One Drop’s BGM using Apple Health, and One Drop will pull InPen insulin data from Apple Health. Educators loved hearing that insulin data will log seamlessly into One Drop, facilitating more informed coaching.

• Insurance coverage for One Drop’s subscription plans “are in the works” and expected within 6-12 months. Currently, these are direct-to-consumer and the pricing appears to have gone up a bit – $24.95/month for one strip per day up to $48.95 for unlimited test strips. The plans include the Chrome BGM bundled in, along with the coaching. For context, mySugr’s pricing is at $39.99 for unlimited strips and coaching, though this positioned as an “promotional price.”

Roche

The Roche booth, which included a section devoted to its SimplePay Savings program, was buzzing with activity. With SimplePay, a vial of 50 strips is just $19.99 cash pay (no insurance), and each incremental 50 strips will add just $10. One booth representative was very excited about Roche’s movement into the ecommerce space, noting that patients will now be able to purchase Accu-Chek BGMs and strips online without a prescription – a huge win for convenience. Indeed, the Accu-Chek site now has a “Home Delivery” option – great to see Roche moving in this consumer-friendly direction, perhaps following some of what has been learned with mySugr’s Bundle program We understandably received no updates on Roche’s recently CE-Marked Solo patch pump, slated for a controlled EU launch this year (Roche 2Q18). Last we heard in July, the pilot launch will start “in the coming weeks” in Austria, Poland, Switzerland, and the UK, to be followed by a “second commercialization phase” in 2019.

Senseonics

The Senseonics team was out in full force advertising the recently FDA-approved 90-day Eversense CGM. Attendees flocked to view live demonstrations of the insertion/removal procedure, and as we’ve now come to expect, the enormous mobile Eversense clinic was parked inside the exhibit hall (we’re not sure if we’re following it or it’s following us...). In between making the rounds at ADA and Keystone, the Eversense bus has been in San Diego and Austin, and is scheduled for upcoming appearances in New York and New Jersey. As a reminder, the very first Eversense shipments/insertions were announced earlier this month, just a few weeks following FDA approval in June. A booth representative was very excited about Senseonics’ first payer coverage for Eversense in the form of Horizon Blue Cross Blue Shield of New Jersey (BCBSNJ), which covers ~four million lives total. During Senseonics’ 2Q18 call earlier this month, we learned that although Senseonics is looking to pioneer a wraparound, category III CPT bundle that would encompass both the supply cost as well as physician time, BCBSNJ has opted to go through DME providers for now along with the new CPT codes (0446T, 0447T, 0448T) for additional provider time associated with the procedures. (Senseonics’ product theater also shared that pharmacy reimbursement is possible, depending on the payer.) Also on the 2Q18 call, CEO Dr. Tim Goodnow shared plans to submit an IDE for the Eversense XL in September, expecting a 180-day US clinical trial to begin “in the coming months.” Although booth representatives were unable to comment on study timing, they did note that others have asked about the trial. We’re not surprised to hear others excited for the 180-day version – while 90 days is certainly compelling, six months without having to change sensors is a huge value-add over current 7-14 day CGMs.

Tandem

Following the very exciting US launch of Basal-IQ on Thursday, Tandem’s gleaming, expansive booth marketed the new predictive low glucose suspend system and G6 integration at its first AADE. A rep told us the first Basal-IQ software update was completed by a t:slim X2 in four minutes at home – WOW! As we reported on Thursday, emails are going out to current X2 users  to update their pumps and add Basal-IQ and G6 compatibility; new t:slim X2 pumps pre-loaded with Basal-IQ are expected to begin shipping by the end of August. Videos playing around the booth nicely demonstrated the predictive suspend feature, with a downward-sloping Dexcom G6 CGM leveling off and avoiding the low – all without alarms or “modes” to manage. Watch the snappy video here on YouTube, which is very well done. Tandem’s very differentiated Control-IQ hybrid closed loop pivotal study (with auto boluses) is also underway,  targeted for a summer 2019 launch. Beyond products, reps told us this year has seen a “totally different conversation” in the booth – not a single question about going out of business, cash in the bank, etc. Indeed, it’s been an incredible 1H18 for Tandem, as shared in the 2Q18 call.

Tidepool

At the Tidepool booth, Mr. Christopher Snider shared that insulin data integration with Apple Health Kit is likely to roll out “soon.” With this update, insulin data from Bluetooth-connected devices will be supported for upload, presumably without the need for company contracts and in a simple, plug-and-play fashion on the patient end. This will be especially compelling for Loop users, which posts data to Apple Health already and could presumably support the HCT-sponsored study on this front. Mr. Snider also highlighted Tidepool’s support of data upload from Medtronic’s MiniMed 630G, 640G, and 670G pumps, released last week. He shared that people are already uploading from their 600-series pumps and that feedback so far has been “positive.” We’re thrilled to see Tidepool continue its relentless push to add even more data sources to its platform, though Mr. Snider rightly pointed out that Tidepool’s offerings are still fairly limited for those in underserved areas. Tidepool continues to work to provide support for additional blood glucose meters to make the software more accessible for cost-conscious users or patients on Medicaid and Medicare.

Valeritas

Valeritas advertised its V-Go patch insulin delivery device. As we’ve heard before, the booth representative estimated that ~90% of V-Go users are type 2s. In her own clinic, she’s found that most of the type 1s who use V-Go were unsatisfied with pump therapy (or found it to be unaffordable) but were reluctant to return to MDI. The booth representative was unable to comment on the status of the Bluetooth-enabled V-Go SIM (Simple Insulin Management) dose capture accessory, slated earlier this month for widespread availability in the US “by the end of 1H19.” As a reminder, V-Go SIM users will be provided with Glooko’s cloud-based mobile and web diabetes data management platform. Next year is going to be an exciting one in this area V-Go SIM will likely launch alongside BD’s Swatch type 2 patch pump (by September 2019), CeQur’s newly-acquired bolus-only Calibra Finesse (mid-2019) and Insulet/Lilly’s U500 Omnipod (“2019”). There’s clearly room for many players here to make insulin delivery safer/easier in type 2.

Voluntis

Voluntis’ booth proudly pointed to the availability of an upgraded version of basal insulin titration app Insulia, which now boasts availability in Spanish. Support for Spanish-speakers is all but a must, particularly in the US: According to the recent press release, the diabetes prevalence among Hispanics in the US is 43% higher than the national average, and a 2014 study found that “52% of Hispanics had poor glycemic control and were at higher risk for cardiometabolic abnormalities than non-Hispanic whites.” In addition, VP of Medical Affairs Ms. Ellie Strock indicated that in addition to rolling out in US clinics, Insulia has begun to make headway and launched/will launch soon in Germany, Canada, and France (where Voluntis’ basal-bolus titration app Diabeo is already on the market). Partnerships (Livongo, Sanofi, Ascensia, Welldoc) and other titration products (NPH, basal-bolus, basal+GLP-1) are moving along, though the team had no specific updates on launch timing to share.

Welldoc

There were two exciting updates to share from our conversation with Welldoc reps: (i) A Spanish version of BlueStar came out on August 13; (ii) Blood pressure cuff and connected scale integrations for the recently-launched hypertension and weight management modules within BlueStar will be coming before the end of the year. This is great news, as the less manual entry, the better – something Welldoc has always needed to improve on. Welldoc now has multiple classes of products: BlueStar Rx, BlueStar, BlueStar C (Consumer), and the Samsung-partnered Diabetes Wellness Program.

• Congratulations to Welldoc’s VP of Clinical Services, Programs and Research, Ms. Malinda Peeples, who took home AADE’s Allene Van Son Distinguished Service Award this year!

• Side note: The lack of capitalization in “Welldoc” is actually intentional, as the company recently underwent a rebranding – check out their updated site!

Diabetes Therapy

AstraZeneca

AZ brought one of the larger booths in AADE’s exhibit hall, highlighting Bydureon BCise (AZ’s new exenatide autoinjector), SGLT-2 inhibitor Farxiga (dapagliflozin), and Xigduo (dapagliflozin/metformin) in equal turn. VR headsets demonstrating how BCise works, which we first saw at ADA 2018, were once again present, and representatives emphasized that they hope BCise will become widely recognized as a beneficial option for both patients currently using Bydureon reconstitution kits (which we heard at ADA will be phased-out starting in September) as well as new patients to the GLP-1 market. Indeed, numbers offered by AZ management during the company’s 2Q18 update indicate this is more or less what’s going on already: Currently, ~half of patients on BCise are new to the GLP-1 agonist class, while ~one-third are coming from the Bydureon pen.

Unfortunately, we didn’t see the SGLT-2/DPP-4 combination therapy Qtern (fixed-dose dapagliflozin/saxagliptin) at the booth (or in AZ’s 2Q18 earnings – the product’s sales have only been broken out once before). When we asked about this impressive product (one co-pay, one dose), representatives explained that copay cards for Qtern are currently unfavorable, making Farxiga and Xigduo XR far more accessible options for patients. This makes sense given current pricing of these drugs but we hope to see greater access shortly. As we wrote during ADA 2018, AZ’s copay card for the suite of dapagliflozin products will cover up to $150 for Farxiga, Qtern, or Xigduo, but Farxiga and Xigduo cost considerably less ($510/month and $551/month, respectively) compared to Qtern ($720/month) at our local CVS in San Francisco. To our understanding, Qtern is actually covered about as well as Farxiga in that, typically when Farxiga is covered, so is Qtern; however, the higher list price for Qtern vs. Farxiga/Xigduo translates to higher out-of-pocket costs for patients, even after the copay card is applied. AZ has additionally referenced provider reluctance to fixed-dose combinations and the lack of flexibility they offer, but management has also reinforced its commitment to Qtern in conversation with us. Interestingly, a representative at AADE noted to us that there could be other departments at AZ that are more focused on Qtern at the moment, outside of diabetes – we’re not sure what this means or what this rep was referring to.

J&J

J&J occupied a smaller, two-person booth devoted exclusively to SGLT-2 inhibitor Invokana (canagliflozin) and fixed-dosed combinations Invokamet/Invokamet XR (twice and once-daily canagliflozin/metformin). Displays and handouts were lined with dense information on canagliflozin, and there seemed to be a particular emphasis on the product’s safety: “Invokana is the only SGLT-2 inhibitor that demonstrated up to 6.5 years of overall safety data.” Indeed, it makes sense that J&J would be keen to reinforce the overall safety of Invokana: On the heels of the amputation signal associated with canagliflozin in CAVNAS (that we feel is not highly relevant to most patients), presented at ADA 2017, and a black box warning for amputations from FDA, Invokana’s value share of the SGLT-2 market has fallen from 34% to 21%. J&J has cited increased discounts, share loss, and higher rebates in explaining its 27% year-over-year loss in revenue (2Q18) from Invokana, and our sense is very much that the controversy over amputations has weakened J&J’s negotiating position and the therapy’s image in the eyes of patients and providers. In our eyes, this is a shame, as we firmly believe (as do, in our observation, most thought leaders) that proper selection for lower-risk patients and vigilant monitoring can minimize, if not eliminate, this risk; so many more patients could benefit from SGLT-2 use, and we’ve been disappointed to see the class’ growth slow in the face of this.

Unfortunately, there was no mention of the remarkable renal/CV outcomes results from CREDENCE, the outcomes trial of Invokana in people with diabetic nephropathy that was stopped ~one year early after canagliflozin met its primary endpoint well ahead of schedule. To be fair, this was announced only ~one month ago, and we’re not even sure J&J has data available in-house – reps certainly should not be speaking to it as marketing at this stage since it is not part of the label. Representatives couldn’t speak to a potential FDA submission for inclusion of data on the label or a novel indication, but we certainly hope this comes soon (we expect a new indication). Moreover, there was no comment on Invokana’s requested CV indication, now expected in 4Q18 after a three-month delay from FDA was announced in July; a positive CHMP opinion on this indication was just announced, and a final EMA decision is expected by the end of the year at least. We assume the delay at FDA is due to bandwidth. We’re curious whether CREDENCE might support a heart failure indication; management has previously stated that J&J will not conduct a dedicated heart failure outcomes trial for Invokana, because key secondary endpoints both include hospitalization for heart failure in a composite and individually measure HHF. It’s not clear to us whether FDA will allow heart failure to be part of a new indication (in our view, there’s certainly a preponderance of evidence that heart failure is significantly improved with SGLT-2 inhibitors), and we could not be more excited to see topline and later full results from CREDENCE.

Lilly

Lilly’s booth was tiny, featuring only two representatives at a medical information station (though the company retained its well-loved espresso station). Next door to Novo Nordisk, Lilly’s lack of a strong exhibit hall presence was keenly felt, though we weren’t surprised to see such a small showing: at ADA 2018, Lilly did not host its own booth, and we also noted very small booths at both ENDO and AACE earlier this year. However, ADA 2018 did feature a large booth from the Lilly/BI alliance, and there was no such exhibit in the AADE hall, which was quite surprising. This means there was no exhibit hall advertising for GLP-1 agonist Trulicity, SGLT-2 inhibitor Jardiance, prandial insulin Humalog, or basal insulin Basaglar. When we asked about the small scale of the booth, representatives cited a “restructuring of strategy” in Lilly’s approach to exhibit halls – it doesn’t seem like they’ll be coming back anytime soon – and hinted at having representatives “virtually” present in the future. Hmm! In many ways, we think this is unfortunate, as exhibit halls can be a key way for clinicians to connect with companies, learn about new products, and get questions answered, and we’re curious for more details on how Lilly made this decision – we’re certainly not the experts on the return on investment.

• No updates were available on Lilly’s newly-launched Diabetes Solution Center, a patient hotline that aims to connect patients with the most affordable option to access Lilly insulin. Representatives at the booth did not have knowledge of any metrics on usage or uptake of the newly launched service. We think AADE would have been an excellent place to raise awareness of this resource in a high-impact way.

MannKind

Just as at ADA, MannKind’s booth featured looping interviews of the outstanding Drs. Anne Peters and Satish Garg endorsing the efficacy and flexibility of ultra-rapid-acting mealtime insulin Afrezza. This flexibility was certainly a theme throughout the exhibit: MannKind’s 2017 TV ad for Afrezza, which stresses the freedom that comes with being able to take insulin at the start of a meal, was also on loop. According to company reps, the ad has run both on national TV outlets and streaming services such as Hulu. As far as we could tell, however, MannKind hasn’t added any info to its exhibit on the positive time-in-range (STAT) or hypoglycemia (AFFINITY-1) results for Afrezza vs. NovoLog, both presented at ADA 2018. Recently on MannKind’s 2Q18 earnings call, CEO Dr. Michael Castagna emphasized that publication and spread of this data will be critical for better physician adoption of Afrezza, and we expect publication of the STAT manuscript any day now – as such, we would expect MannKind’s promotional materials to make a bigger deal out of this data in the future.

Also a potential tailwind for physician and patient adoption of Afrezza is BluHale, MannKind’s Bluetooth-enabled inhalation monitor and accelerometer, currently under distribution as an in-clinic training tool for Afrezza. We asked what’s next for BluHale, and representatives offered that the device has great potential to become a standalone revenue driver in future iterations. However, we think the primary focus will and should remain on building better access, recognition, and utilization of Afrezza in the first place – the product sold <$4 million in 2Q18, and MannKind needs a larger user base before BluHale can really drive revenue growth. Features to be included in coming updates are not set, but representatives did highlight currently-existing connected devices from which MannKind could draw inspiration; these include Companion’s InPen, which includes a dosing calculator and provider access. We personally would love to see a much more robust and aesthetically pleasing connected app featuring dose calculation, blood glucose and dose logging, and smooth downloading/connection for providers in the future, which could offer real value and convenience to patients who want these options.

Merck

Merck chose to dedicate half of its booth to the Januvia franchise, splitting the remaining panels between Pfizer-partnered Steglatro and the Pneumovax 23 vaccine. The booth was quite sizable but characteristically pared-down; Merck doesn’t put a much emphasis on taglines and branding, featuring only two double-sided informational panels. We asked a couple of reps about coverage for Steglatro and Steglujan (the fixed-ratio Steglatro/Januvia combination), and they offered that Merck isn’t especially promoting one or the other. Right now, they said, reimbursement is still very limited because the product is so new. But once Merck/Pfizer have a chance to negotiate better formulary access for 2019, reps expect Steglatro and Steglujan will have equivalent coverage and copays because that is, historically, what happened with Januvia and Janumet. While it was surprising at the time to see both priced at the same level, we would be surprised to see the list price for an SGLT-2/DPP-4 combo also at that level. We are not sure if we misunderstood the rep – presumably there is a “gap” where the SGLT-2/DPP-4 combination could be priced higher than the branded agent with metformin (Janumet) but lower than competitive branded combos -  AZ’s Qtern and Lilly/BI’s Glyxambi.

We do think Steglatro could have a leg-up in terms of gaining access, and it’ll need one as the fourth SGLT-2 to enter the market: Merck reps have previously highlighted that Steglatro’s list price is ~42% lower than that of other standalone SGLT-2 inhibitors (J&J’s Invokana, Lilly/BI’s Jardiance, and AZ’s Farxiga). Last we checked, the list price for Steglatro at our local San Francisco CVS was $319/month or $10.63/day, compared to ~$17/day on average for Invokana, Jardiance, and Farxiga. Wholesale price has been confirmed to us as $270/month, which is exciting since the copay card for ertugliflozin products covers up to $460/month, ostensibly making Steglatro free for many commercially insured patients. At $520/month, however, Steglujan is another story and would cost ≥$60/month with a copay card, after a pharmacy markup on the wholesale price. We are, however, excited that Merck reps have suggested the company will bolster commercialization efforts around Steglujan as payer coverage grows. To be sure, real-world uptake of SGLT-2/DPP-4 fixed-dose combos has been disappointingly low so far (the class also includes Lilly/BI’s Glyxambi and AZ’s Qtern), and we’re hoping the whole field doubles down on education for both patients and providers.

Merck also debuted its diabetes management and engagement platform, map4health, developed in collaboration with Healthy Interactions, a population health company specializing in chronic disease management and education. Map4health is designed to facilitate in-person counseling, intended to be used as a standalone tool or integrated into existing DSMES programs. Providers can use the dashboard to view patient data trends and to communicate with their patients. Pharmaceutical companies are increasingly turning towards technology to enhance and expand their offerings – we’ll be interested to see how Merck handles the digital space and whether this launch signals a new focus on telehealth and coaching for the company.

Novo Nordisk

Novo Nordisk’s booth most prominently featured new GLP-1 agonist Ozempic, which took up all of the exterior overhead space and occupied the main promotional real estate inside the exhibit; location wise, the booth was positioned squarely at the main entrance to the hall. Informational panels also advertised Victoza, Tresiba, and Xultophy, and some information on Fiasp was also to be found within the booth. A rep estimated that Ozempic access is currently at ~65-70% in the US (though this doesn’t speak to the quality of reimbursement) and seemed genuinely excited about how the product launch was going. This is more or less on par with what Novo Nordisk management indicated in the company’s recent 2Q18 update, where we heard that most districts in the US have switched over from Victoza to Ozempic promotion; in 2Q18, Ozempic sold $31 million, vs. $898 million sold by Victoza. Our overall sense from the meeting was that CDEs weren’t necessarily that familiar with Ozempic as of yet (or really with GLP-1 agonists generally) but were also excited about the improvement over previous options that Ozempic offers. We also couldn’t help but express our enthusiasm for Xultophy (insulin degludec/liraglutide), and reps highlighted results from DUAL XII, which demonstrated that Xultophy gives equal A1c-lowering as traditional basal-bolus therapy – and also causes weight loss, whereas basal-bolus gives weight gain. We continue to see so much room for Xultophy (and Sanofi’s similar product, S0liqua) to grow and reach more patients, but a rep did highlight a barrier to uptake that we don’t typically think of: Xultophy has an upper limit on 50 units of basal insulin, so it’s not always an ideal option for patients on very high basal insulin doses, who might be more frequently considered for this treatment intensification option. On the flip-side, adding the GLP-1 agonist can allow for significant reduction in basal insulin requirements, and, as the rep emphasized, it’s always good to avoid the added danger of hypoglycemia that comes with rapid-acting insulin.

Salix

At ENDO 2018, the great Dr. James Gavin referenced a little-used insulin sensitizer, Salix’s Cycloset. The oral dopamine receptor agonist (bromocriptine mesylate) has been around for decades (initial US approval 1978, but this indication was approved in 2009), and Dr. Gavin focused on the therapy’s one-year CVOT (n=3,095 patients with type 2, published in 2010). That trial found an encouraging 42% risk reduction on a composite CV endpoint (HR=0.58, 95% CI: 0.35-0.96), and a rep at ENDO told us that a superiority-powered CVOT was in the works. Unfortunately, the company rep at AADE had no knowledge of this trial and actually doubted that one would be conducted, given the associated cost (it was conducted, as Dr. Gavin said, years back, as far as we know). We did get the sense that Salix promotes this CV finding – the drug is not particularly easy to take – it is multiple doses a day, which tends to impact adherence. Another rep also emphasized that Cycloset isn’t a good option for patients later in the course of disease, for example, just before the initiation of insulin; as an insulin sensitizer, Cycloset won’t be very efficacious in patients with lower endogenous insulin production, though it could help those who are taking insulin need lower doses. We also got the sense that some of the data behind the therapy isn’t as strong as it could be: In the CVOT, Cycloset gave a 0.5% placebo-adjusted A1c decline over 52 weeks in participants on one-two background therapies, which the rep likened to the effect of DPP-4 inhibitors – though Cycolset certainly doesn’t have the same tolerability profile (more on that below) that DPP-4s offer.

We were struck by the fact that the target dose of Cycloset is four to six pills per day, titrated over as many weeks and taken with food. In our view, taking that many pills every morning is a pretty significant burden on patients, and dosing isn’t very flexible. As Dr. Bill Polonsky has argued, people don’t like taking medications chronically because it makes them feel “sick”, and we imagine taking ≥four pills a day is an issue for many patients; we’re curious whether it would be possible to formulate a higher-dose pill to cut down on that burden. Additionally, Cycloset is associated with nausea: In the CVOT, 32% of participants experienced nausea with the therapy vs. 8% on placebo; however, this does subside over a few weeks, reminiscent of GLP-1 agonists, and Dr. Gavin suggested slower titration in clinical practice would ameliorate this issue. We also suspect that many HCPs simply aren’t comfortable prescribing a medication that acts directly on the brain and dopamine receptors. Though patients with type 2 diabetes do have decreased dopamine receptor activity in the morning, this isn’t a part of pathophysiology that most HCPs are used to treating in diabetes.

In terms of access, Cycloset reimbursement apparently varies by region in Medicare Part D, and Salix offers a $0 copay card for patients with commercial insurance. In trying to explain low utilization, the Salix rep offered that there just aren’t a lot of prescribers who think to give Cycloset to patients, especially not early on in the course of disease when it can be most effective. Ultimately, given the relative dearth of insulin sensitizers on the market (TZDs are the only current option, and these come with considerable baggage), we do think it’s a shame that Cycloset seems to be more or less disregarded but from our view that is driven by poor usability – the number of doses a day for patients who don’t like acknowledging their diabetes makes it hard to usue. Unsurprising to us is that Dr. Ralph DeFronzo, who frequently decries the lack of available insulin sensitizers and underutilization of TZD pioglitazone, has written about and conducted research on Cycloset – the fact that we can’t recall hearing him mention the therapy in any of his characteristic talks on treatment strategies and combination therapy suggests he also thinks adherence would be low. Overall, in our assessment, there’s a storm of small but mighty scientific, commercial, and clinical headwinds in the way of greater utilization of this therapy, and it will likely take a sizable investment from Salix to overcome them.

Sanofi

Sanofi’s exhibit hall booth primarily featured Lantus (basal insulin glargine), Toujeo (next-gen basal insulin glargine), and Soliqua (insulin glargine/lixisenatide). Large touch screens were available to scroll through detailed information touting the benefits of each product, and the material for Toujeo placed a particular emphasis on the product’s potential to reduce hypoglycemia compared to Lantus. Sanofi continues to position Soliqua as an intensification option for patients not meeting A1c goals on basal insulin alone, as per its FDA indication. There was also an interactive component in which attendees could explore the options of either titrating insulin or initiating Soliqua for a patient not hitting their target A1c with basal insulin alone. As always, Sanofi’s smoothie station was a big hit with attendees; however, we were more excited to hear reps focus on the benefits of avoiding hypoglycemia, particularly for patient quality of life.

Xeris

Xeris’ robust glucagon pipeline was the focus of its small, one-man booth; a large touchscreen featured the company’s clinical-stage pipeline, headlined by the Glucagon Rescue Pen, which was recently submitted to FDA for review (decision expected ~2Q19-3Q19). During Xeris’ highly successful June IPO (which raised $89 million for the company – a full $21 million more than expected), we were excited to learn about a new phase 1 dual-hormone AID study using Xeris’ room-temperature-stable glucagon formulation (XeriSol), led by OHSU’s Dr. Jessica Castle and mentioned in Xeris’ booth. On Monday, Xeris issued a press release about this study (n=19), which is now recruiting and should be complete by June 2019. As noted by Xeris, dual-hormone systems have been enabled by the advent of liquid-stable glucagon, and co-administration of insulin and glucagon can allow for the minimization of both hyperglycemia and hypoglycemia. It’s also possible that these systems will enable more aggressive insulin infusion, with the glucagon safeguard in place, which could give them an edge over insulin-only closed loop systems. The other major dual-hormone system in development, Beta Bionics’ iLet Gen 4, is using Zealand’s dasiglucagon; a pivotal trial for that system is slated for a June 2019 start.

Of note, when we asked about the company’s recent trademarking of the name “MyGluca” for the G-Pen, the representative shared that several names have actually been trademarked and submitted to FDA, and the company will choose from among those that get the OK from the agency. See all the names here – in our opinion, MyGluca is the snappiest, but GlucaXer and HypoGlu also have a certain ring to them! Finally, we’re eagerly awaiting more info on the company’s preclinical pramlintide/insulin co-formulation, which we learned about in June from the company’s IPO filing; an IND is expected during 2H18, and the company doesn’t have any additional updates at this time.

--by Maeve Serino, Brian Levine, Martin Kurian, Peter Rentzepis, Ann Carracher, Adam Brown, and Kelly Close