ATTD (Advanced Technologies and Treatments in Diabetes) 2020

February 19-22, 2020; Madrid, Spain; Day #4 Highlights - Draft

Executive Highlights

  • ATTD sped through the finish line, ending with a half-day on Saturday! See below for our top eighteen highlights and make sure to check out our reports from days #1, #2, and #3!

  • We got to hear the much-anticipated pilot data from Jaeb, the Helmsley Charity Trust, and Cecelia Health’s “Geek Squad” virtual diabetes clinic, which remotely initiated 36 patients with diabetes on CGM. Impressively, study participants (27 type 1s, 7 type 2s) used the device an average 95% (6.9 days/week) of the 12-week study period and saw a statistically significant -1.1% decline in A1c from 8.3% at baseline. WOW! This is beyond what we had expected.

  • Onduo’s Dr. Ronald Dixon presented positive real-world satisfaction data from n=594 patients with type 2 diabetes, continuing the trend of novel methods to deliver care. On a five-point Likert scale (1 = strongly disagree; 5 = strongly agree), average overall satisfaction came in at a heartening 4.5. Promisingly, 80% of participants also reported that they were comfortable with CGM insertion on remote education alone, and Dr. Dixon anticipates this number will rise as Onduo continues to refine its practice.

  • An ancillary analysis from CONCEPTT found that achievement of target CGM and A1c goals during pregnancy with type 1 is difficult to achieve, even for those on use real-time CGM. Furthermore, statistically significant improvements in Time in Range and A1c in real-time CGM compared to blinded CGM (control) were only seen in the third trimester. Correlative analysis also showed that A1c is a better predictor of negative pregnancy outcomes than CGM metrics. 

  • OHSU’s Dr. Jessica Castle delivered an intriguing presentation on the accuracy of the Dexcom G6 compared to SMBG during aerobic, resistance, and high intensity exercise. Impressively, the mean absolute relative difference (MARD) did not change for any type of exercise – before, during or after. MARD was significantly affected only at 45 minutes for aerobic exercise and at 30 minutes for resistance training, otherwise the measure went unchanged throughout the study.

  • Outside of technology, Dr. Jay Skyler bookended the meeting with a sweeping, optimistic overview of the type 1 cures landscape, with a particular focus on beta cell replacement. It’s remarkable the range that he showed in both talks. Dr. Skyler mentioned several private and public sector initiatives in beta cell replacement efforts, highlighting ongoing work at Orgenesis, ViaCyte, Semma, Novo Nordisk, Lilly, and others. Regarding Orgenesis, Dr. Skyler provided the first update we’ve heard on the company’s progress in quite some time, noting that human clinical trials for its autologous stem cell research is expected in 2020/2021.

ATTD 2020 rolled to the finish with a half-day on Saturday! See all our highlights below and make sure to check out our coverage of the first three days.

ATTD Day #1 HighlightsDr. Battelino: put DCCT in “history part” of your brain, Dr. Bergenstal: FNIR; Medtronic cost-savings data with iPro 2 CGM; opening ceremony

ATTD Day #2 Highlights – 18 highlights across CGM, AID, decision support, drugs, and big picture: WISDM extension data, Dexcom G6 in pregnancy, Control-IQ 6-14 years, Advisor Pro study + more

ATTD Day #3 Highlights – 27 highlights: Loop observational study at 6-months, iDCL3 Control-IQ extension, new Medtronic 7-day infusion set, ATTD Yearbook, + more

Table of Contents 

Diabetes Technology Highlights

1. “Virtual Speciality Clinic” Pilot Study (n=36) Affirms a Promising Future Where Remote Onboarding of CGM is Possible (and Successful!): 95% CGM Wear, 1.1% A1c Reduction After 12 Weeks (Baseline 8.3%)

As promised at the 2019 AADE Technology Summit, Northwestern’s Dr. Grazia Aleppo unveiled encouraging pilot data (n=36) from the Jaeb/Helmsley/Cecelia Health “Virtual Speciality Clinic” virtual, diabetes clinic. Impressively, study participants remotely initiated on CGM (n=27 type 1s, n=7 type 2s) – including prescription, shipment and education – used the device an average 95% of the time (6.9 days/week) during the 12-week study period and saw a statistically significant -1.1% decline in A1c from 8.3% at baseline. Time in Range, estimated from A1c at baseline, also jumped from 48% to 59% (p<0.001) over the 12 weeks. Unsurprisingly, the participants with highest baseline A1cs saw the greatest benefits from CGM: those with A1c >9% at baseline saw a 1.8% A1c reduction with CGM; those with A1c <7.5% at baseline saw a 0.4% A1c reduction. Furthermore, patient-reported questionnaires showed increases in glucose monitoring satisfaction, trust, and diabetes technology attitudes, as well as decreases in diabetes management distress, emotional burden, and behavioral burden. Dr. Aleppo further specified that the clinic seeks to address the fact that a huge proportion of people with diabetes are only treated in the primary care setting and thus have little access or education to the latest in diabetes technology, pointing to PCP-treated patients with type 1 as a target population. Looking to the future, Dr. Aleppo confirmed that a larger study to evaluate the model is in the works (200-300 people in 5+ states in late 2019 or early 2020, as of June 2019).

  • Study participants were able to choose between the Dexcom G6 (n=31) and FreeStyle Libre CGM (n=3) based on recommendations from a short questionnaire. In terms of insulin delivery, seven participants were on a pump and 27 on MDI.

  • Three virtual visits with Cecelia Health CDEs were held: (i) initial training on insertion, how to set alerts, how to download data; (ii) an appointment ~two weeks after initiation to review CGM data and develop any recommendations; and (iii) a visit at ~four weeks to discuss tips and tricks to optimize CGM use. At ADA, we heard that “Geek Squad” made 14 check-ins with participants, helping review CGM data and provide actionable insights, along with mental health support; it’s unclear what exactly constituted a “check-in.” (This was the first study to remotely onboard and support people with CGM, so the team erred on the side of too many touchpoints.) In larger study, the number of check-ins will be reduced, to give the program a better chance at scaling.

  • Study participants were recruited from the Wisconsin Research and Education Network and recruited by mail, using a link to the study website. Again at ADA 2019, we heard that about 80% of letter recipients went online and registered for the study without a follow-up phone call, demonstrating a desire for a service like “Geek Squad.”

  • We first caught wind of the Jaeb/HCT/Cecelia virtual diabetes clinic at JPM 2019. There, Helmsley Trustee Mr. David Panzirer noted, “I think about a model like Best Buy’s Geek Squad. Imagine a dedicated team of professionals to help people get on diabetes technology…How could we get people with diabetes straight to the Geek Squad (company agnostic) to help them with technology? We need a new model; the current model is failing.” We’re thrilled to see a pilot of Mr. Panzirer’s aspirations come into fruition and look forward to even more work on a future where patients feel able to tap into the life-changing power of CGM from the comforts of their own home.

  • Assuming “Geek Squad” continues to drive improved adoption and outcomes, we’re curious who might be interested in funding the Squad. With healthcare providers, especially primary care physicians, “Geek Squad” would handle the burden of prescription and initiation of CGM for patients while also improving patient outcomes. For device manufacturers, a device-agnostic group like “Geek Squad” would be able to increase sales of devices without manufacturers having to manage large clinical teams – especially in more remote areas. With cost-savings data, it’s certainly possible that payer could also be interested.

2. CONCEPTT Analysis Shows Pregnant Women with Type 1 Diabetes Struggle to Meet Target CGM and A1c Goals; A1c Better Correlated with Pregnancy Outcomes than CGM

Using data from the CONCEPTT trial, Spain’s Dr. Diana Tundidor evinced that it is still difficult for pregnant women with type 1 to achieve target glycemic goals even with the help of real-time CGM (RT-CGM) wear. According to the consensus document drafted at ATTD 2019, and subsequently the ADA 2020 Standards of Care, pregnant women with type 1 diabetes have lower CGM metric targets: (i) <25% time above range (>140 mg/dL; TAR); (ii) >70% Time in Range (63-140 mg/dL; TIR); (iii) and <4% time below range (<63 mg/dL; TBR). Though TIR was found to increase over the course of pregnancy, only 8% of study participants reached target TIR during the first trimester (n=226), 10% at Weeks 24-25 (n=203), and 35% at Weeks 34-35 (n=177). Furthermore, a statistically significant improvement in TIR for study participants using real-time CGM rather than masked CGM (control) was only seen during the third trimester. While only a limited proportion of women achieved any of goal ranges during the study, Dr. Tundidor explained that she believes an earlier commitment to reaching target values will be the biggest help in improving these rates of attainment, rather than simply making the goals less stringent. Regardless, it’s clear that gestational diabetes is an area of much needed research, and given the increased roll out of CGM in diabetes, we especially hope to see real world data soon. 

  • In addition, goal achievement was linked to a number of improved pregnancy outcomes. Achieving TAR goals (>140 mg/dL) at Weeks 34-35 was associated with reduced risk of preterm birth and large for gestational age (LGA) birth, and meeting target TAR at Weeks 24-25 was similarly associated with lower rates of LGA. Surprisingly, achieving target TBR (<63 mg/dL) at Weeks 24-25 was associated with an increased risk of neonatal hypoglycemia and neonatal intensive care unit (NICU) admission. In order to further investigate the effects of TBR, Dr. Tundidor’s group then analyzed combination TIR and TBR, finding that co-TIR+TBR achievement was associated with reduced risk of LGA at baseline and Weeks 34-35.

  • In terms of target A1c goals, the ADA 2020 Standards of Care recommends a value of 6.5% for the first trimester, followed by 6.0% during the second and third trimester. Results between TIR and A1c were comparable, and again, a statistically significant benefit for those on real-time CGM was only demonstrated in the third trimester (31% at target vs. 17% on masked CGM, p=0.032). Interestingly, A1c was found to be superior to CGM values in the prediction of pregnancy outcomes. Achieving the target 6.0% at baseline was associated with decreased risk of LGA. Meeting the target of 6.5% at Weeks 24-25 correlated with decreased preterm birth, LGA, neonatal hypoglycemia, and NICU admission, while attaining target A1c at Weeks 34-35% was only linked to decreased preterm birth, LGA, and neonatal hypoglycemia.

3. Real World Study of Connected NovoPen 6 in 39 Pediatric Type 1s Shows Significant Reductions in Daily and Nocturnal Hypoglycemia, No TIR Difference

Dr. Peter Adolfsson (University of Gothenburg) presented encouraging results from a real-world trial of Novo Nordisk’s NovoPen 6 in the pediatric type 1 population, demonstrating significant reductions in daily (-31%, p<0.0001) and nocturnal (-24%, p=0.043) hypoglycemic episodes after 12 months. Hypoglycemic episodes were defined as glucose levels <54 mg/dl for at least 15 minutes. Data were based off of collected CGM metrics – notably, Time in Range and time in hyperglycemia were not significantly improved with use of the connected pen.


  • Study design and objective: The study aimed to describe evolution of glycemic parameters following introduction of the connected insulin pen in a pediatric population. Children <18 years old with type 1 (n=39) were enrolled and prescribed connected insulin pens for basal and/or bolus insulin injections across three pediatric diabetes clinics in Sweden. Mean age of the participants was 13.5 years. HCP visits for patients were conducted according to standard clinical practice (about once every six months) and insulin pen data was uploaded during clinic visits or at home via Glooko/diasend. Patients did not review data outside of clinic visits, where data was reviewed with HCP and changes to insulin regimens were made accordingly.

  • At baseline, participants experienced a mean of ~0.5 hypo episodes (<54 mg/dl for >15 minutes) per day. After >12 months using the connected NovoPen 6, the rate of hypo episodes fell to ~0.3/day, a 31% relative reduction (p<0.001). This is a really big deal. The percent time spent <54 mg/dl also showed a relative reduction of 14% after 12 months (p=0.03), though the baseline was not given. Time in Range did not change significantly from baseline (51%), nor did time >180 mg/dl (42%). Overall, these results are somewhat surprising as the results showed significant increases in the total daily dose of insulin, particularly the mean basal dose, which rose by 12% after 12 months compared to baseline. 

  • Previous work from a trial of the NovoPen 6 in adults (presented at two posters at ADA 2019, n=94 at 12 Swedish sites) showed more promising results. Two-weeks of CGM metrics at follow-up (14 days after the final clinic visit) were compared to two-week baseline metrics (14 days following obtaining the pen). Compared to baseline, mean time-in-range improved from 38% to 46% (+1.9 hours/day), driven by time >180 mg/dl decreasing from 49% to 42% (-1.8 hours/day). 81 adults were included in an adherence analysis, which showed a very impressive 43% fewer missed meal boluses (baseline: 0.74/day) using the connected pen.

  • As a reminder, the NovoPen 6 and Echo Plus are already CE-Marked and a launch beginning in Europe is expected in 2Q20. The reusable NovoPen 6 and Echo Plus will display the last insulin dose and time on their ends, have an 800-dose memory, and five-year battery life. Data from the pens can be downloaded with NFC and the pens are compatible with both basal (Levemir, Tresiba) and bolus (NovoLog, Fiasp) insulin cartridges. The NovoPen 6 will allow adjustments down to 1 U with a maximum 60 U dose, while the pediatrics-targeted Echo Plus will allow adjustments down to 0.5 U with a maximum 30 U dose. 

 

4. Session on Real-World Evidence Highlights Low Achievement of Time in Range Targets in the Diabetes Population

In a session on real-world evidence (RWE), Dr. Irl Hirsch (University of Washington) provided a deep dive on the available real-world CGM data on Time in Range targets in the diabetes population. Based on the available studies (summarized in the chart below), it is estimated that real-world Time in Range (TIR) is ~51%-65% for people with type 1 diabetes and ~62%-69% for people with type 2 diabetes. Similarly, the % coefficient of variation (%CV) for glucose is ~35%-45% in type 1s and ~29%-30% in type 2s. We’ve also taken our stab at estimating the population’s average Time in Range and come out with similar, perhaps slightly lower, estimates. Dr. Hirsch underscored that there is vast room for improvement here (especially given that the people in these studies were using CGM and therefore likely had better TIR than those without), but the recommended targets for TIR and %CV (>70% and <33% respectively) are well within reach. On the issue of Time in Range, Dr. Hirsch also discussed how measured A1c can vary from CGM-predicted A1c (Glucose Management Indicator, GMI). According to a study of CGM users in his own clinic (n=717), over 50% of patients had an A1c >0.5% off from the CGM-predicted value, and 22% were 1% off. This discordance is extremely concerning, and Dr. Hirsch pointed out that an A1c mismatch of 0.5% is “concerning” and a 1.0% difference is clinically significant. A larger issue is how measured and estimated A1c values will be interpreted as not all clinicians are aware of this difference. As Dr. Hirsch put it, “which one are patients, physicians, and payers supposed to accept?” As CGM use becomes more widespread, this is an issue that the field will have to confront.

  • Turning to pediatrics, Joslin’s Dr. Lori Laffel underscored that real-world evidence points to vast unmet needs in the adolescent type 1 population. A recent study showed that only 14% of children using CGM and MDI and 28% of children using CGM and an insulin pump achieved Time in Range >70%. Similarly, only 17% and 26% respectively achieved the percent time above 180 mg/dl goal of <25%. Dr. Laffel offered several suggestions for how to improve this situation – namely increasing the use of CGM (encouragingly, CGM use has risen from 7% of the type 1 population in 2012 to 30% in 2018), including exercise as part of routine activities, improving our understanding of how macronutrients affect Time in Range, and improving AID systems.

 

  • Earlier in the session, UCSF’s Dr. David Klonoff set the stage with a discussion of what exactly constitutes real-world evidence (RWE). As he put it, as opposed to a randomized control trial (RCT) which assesses whether an intervention can work under ideal conditions and has been considered the “gold standard” to evaluate the efficacy of the treatment, RWE addresses whether an intervention can work under usual clinical practice conditions. RWE can come from a variety of sources (consumer data, disease registries, survey data, electronic health records, insurance claims, etc.), and is subject to selection bias and reporting bias, but in many cases these are much more feasible than a RCT because they save an incredible amount of time and money. Unlike a RCT, a pragmatic RWE trial offers the intervention to all participants by using usual care as the comparator group and helps identify unanticipated and often rare complications.

5. IDC’s Ms. Mary Johnson Details Hypoglycemia Rates in DCCT/EDIC Cohort Wearing FreeStyle Libre Pro

International Diabetes Center’s highly regarded Ms. Mary Johnson presented follow-up data from the landmark DCCT/EDIC trial to understand Time in Range using Freestyle Libre Pro CGM, building off of a similar presentation at EASD 2019 by Dr. Rose Gubitosi-Klug. The headline result was that the number of participants reaching Time in Range is poor, and that there is a clear trend of nocturnal hypoglycemia, which is improved by a higher A1c, prior use of pumps/CGM, and non-smoker status. In the original DCCT, hypoglycemia was far worse in the intensive blood glucose control group, and in EDIC, there was a small group of ‘frequent fliers’ who experienced significantly more hypoglycemia. In this study, the n=765 participants (who are now on average 59 years old!) wore a Freestyle Libre Pro for ~twelve days. Their average A1c at baseline was 8.0%. Time in Range was only 52% for all participants and time below 54 mg/dl was 4%. Interestingly, there was a pattern of nocturnal hypoglycemia – time below 54 mg/dl was 4% during the day and 7% during the night (note that the target is <1%, as detailed in the ADA 2020 Standards of Care). While 11% of participants experienced no hypoglycemia, a group of 7% of people experienced >21 episodes of hypoglycemia per day. Although users of pumps and CGM (including insulin suspend pumps) had less hypoglycemia and better Time in Range overall, the entire cohort still has a long way to go to reach the recommended targets. We do note however that FreeStyle Libre Pro does tend to overread hypoglycemia (per the label), so true outcomes may be slightly better.

  • By the end of the original DCCT study, 65% of the intensive therapy group experienced severe hypoglycemia, compared with only 35% of the control group – not surprising given the challenges of insulin therapy. In the EDIC follow-up, 50% of each group had severe hypoglycemia, which was running at ~0.4 events per patient year on average. However, 7% of EDIC participants experienced 30% of all episodes.

  • Overall there was concerningly high levels of clinically significant hypoglycemia and a subset of participants had worryingly high frequency and duration. 7% of participants experienced more than 21 separate events below 54 mg/dl during the study (see table), reminding us of the “frequent fliers” in EDIC. Furthermore, 38% experienced at least one hypoglycemia event (<54 mg/dl) lasting for two hours or more during the day, and 52% at night.

# Episodes of Hypoglycemia

% of Participants

0

10.6%

1-10

60.9%

11-20

21.4%

>21

7.1%

  • On average, users of insulin suspend pumps (presumably Tandem’s Basal-IQ or Medtronic’s 640G and 670G) had on average of ~7% more Time in Range, lower rates of hyperglycemia, and improved time spent <54 mg/dl. They were still some way from the target of 70% Time in Range and <1% time below 54 mg/dl.  (see photo).

  • Only 9% of participants met the Time in Range targets, and only 30% achieved the 4% goal for <70 mg/dl and 28% the 1% goal for <54 mg/dl. The percentage of time spent below 70 mg/dl trended smoothly with A1c and smoking status. Study participants with higher A1cs experienced less hypoglycemia, as did the non-smokers. The group at target (<4% below 70 mg/dl) had a mean A1c of 8.3%. Furthermore, use of pumps and CGM was significantly associated with less time spent below 70 mg/dl, although the trend was not compelling. The percentage of time over 250 was extremely worrisome at over 17% - this was on top of a full 40% plus at over 180.

6. Dr. Roy Beck Reviews Relationship Between TIR and Complications, Argues for TIR Over A1c in Clinical Trials

Dr. Roy Beck (Jaeb Center) provided an overview of the association between Time in Range and various diabetes complications, calling for greater use of Time in Range over A1c in future clinical trials. Dr. Beck’s own 2018 Diabetes Care paper delved into DCCT data from 1983-1993, computing approximate Time in Range from seven-point glucose measurements. The 7-point glucose profile measures glucose pre- and 90-minute post- meals and at bedtime on the same day every three months. Over this 10-year period, for each 10% drop in Time in Range, retinopathy progression rate increased by a whopping 64% and the risk of microalbuminuria increased by 40%. Dr. Beck pointed out that using A1c instead of percent Time in Range to examine the rising rates of complications produced nearly identical results, a kind of validation for the legitimacy of using Time in Range in this context. Another 2018 study, Lu et al. found a significant relationship between Time in Range and retinopathy in people with type 2 diabetes (n=3,262). For those with >86% Time in Range, the prevalence of vision-threatening retinopathy was only 3.5%, vs. 9.7% for those with <51% Time in Range. Furthermore, mean Time in Range decreased according to retinopathy severity, from 68% for those with no retinopathy to 64% for mild retinopathy, 58% for moderate retinopathy, and 59% for vision-threatening retinopathy (p<0.001). Of course, while these data are compelling, both studies had only limited data (one day of seven measurements ever 3 months in the DCCT, and only 3 days of CGM data in the Lu et al. study). To this end, Dr. Beck praised upcoming trials such as PERL (Preventing Early Renal Loss in Diabetes) and the DRCR Retina Network Fenofibrate Protocol, which incorporate blinded CGM in the study design for up to 10-14 days every 6 months to assess the impact of Time in Range on kidney disease and retinopathy, respectively. According to Dr. Beck, a growing body of evidence suggests that there is a stronger association between vascular complications and longitudinal CGM measurements. This presents a compelling case for regulators to accept CGM and Time in Range as a meaningful endpoint for clinical trials. He ended on a provocative note: “A1c is a surrogate measure for glucose, but with CGM the actual glucose content is measured. Do we still need a surrogate?”

 

7. Onduo Delivers Stellar Real-World Satisfaction: 80% of Participants Comfortable with CGM Insertion Purely from Virtual Education

Onduo’s Head of Clinical Affairs Dr. Ronald Dixon provided a glimpse into the company’s ongoing mission to provide virtual care to individuals with type 2, with real-world satisfaction data from n=594 patients. Program participants were clinically evaluated, prescribed, and mailed Dexcom G5 or G6 CGM devices by Onduo’s virtually accessed team of CDEs and licensed endocrinologists. On a five-point Likert scale (1 = strongly disagree; 5 = strongly agree), average overall satisfaction came in at a heartening 4.5. More than 95% of survey participants reported that CGM taught them the impact of daily habits and eating and that CGM made it easier to perform self-care behaviors. Very promisingly, 80% of participants also reported that they were comfortable with CGM insertion, and Dr. Dixon anticipates this number will rise as Onduo continues to refine its practice.

  • Onduo’s survey boasted a relatively diverse study population, compared to those who have traditionally accessed CGM. Of the participants, 60.8% voted that they were “previously unfamiliar with CGM,” reflecting that remotely onboarding patients with no knowledge of CGM is possible. In addition, 72.4% were from urban settings, and 27.6% were from rural settings.

  • On top of the compelling survey results, study participants also saw significant improvements in A1c – particularly for those with a high A1c at baseline. Participants with a baseline A1c >9.0% (n=57) demonstrated a -2.6% reduction (p<0.001) over a mean follow-up of 10.2 months, and the overall decrease was -0.6% ± 1.5 (p<0.001). These results further corroborate A1c benefit documented in a December 2019 paper, published in the Journal of Diabetes Science & Technology.

    • In terms of segmentation, Dr. Dixon specified that Onduo hopes to help individuals with an A1c >8.0% decrease their blood glucose levels using medication and behavioral optimization. For those with an A1c already <8.0%, the company will “rinse and repeat” with CGM and HCP recommendations to prevent any future rises.

  • In the company’s simultaneously-published press release, Dr. Richard Bergenstal, a collaborator on the study commented: “These data serve as a very robust demonstration that it is feasible to ship CGM to people with type 2 diabetes, train them on how to use the system virtually, and derive significant value from its use. A majority of these people were not previously familiar with CGM, suggesting that approaches like that used by Onduo can broaden access to this transformative technology.”

8. Dexcom G6 Matches SMBG Accuracy During Exercise in n=24 Study; TIR Data to Be Published at Later Date

OHSU powerhouse Dr. Jessica Castle presented a CGM in exercise study of n=24 adults with type 1 diabetes on MDI, comparing results from self-monitoring of blood glucose (SMBG) and the Dexcom G6 during exercise. Average age was 31 years old, and baseline A1c was 8.8%. The participants were randomized to three exercise types – aerobic, resistance, and high intensity. As expected, glucose dropped on average after exercise, by 47 mg/dl in aerobic and around 20 mg/dl in the other two types. Importantly, the mean absolute relative difference (MARD) did not change for any type of exercise – before, during or after. MARD was significantly affected only at 45 minutes for aerobic exercise and at 30 minutes for resistance training, otherwise it was not different. Excitingly, Dr. Castle noted that Time in Range is in fact the primary outcome of the trial, however this data will be presented at a later date.

  • Study participants exercised using a prepared video of exercises, and an Apple Watch was used to track the exercise. The Dexcom G6 was worn on the abdomen, replaced every ten days, and sensors were not calibrated. Two in-clinic exercise sessions were performed on day nine and day 16 of the trial, roughly half-way through the sensor life. A Contour Next meter was used for capillary blood glucose testing.

  • Impressively, a Clarke Error Grid showed that all the aerobic and high intensity points were in the A and B regions, and all but two of the resistance points were inside A and B. As a reminder, region B is considered to be an “inaccurate” point, but that would not lead to inaccurate treatment.


  • Dr. Castle began her talk by stating that CGM is “now the standard of care for managing type 1 diabetes”. We agree that CGM should be the standard of care, but reimbursement still has a ways to go and even more important is provider awareness – very low.

Selected Questions and Answers:

Q: Isn’t it better to call it a ‘difference’ rather than an ‘error’?

A: I agree completely, and if I had more than ten minutes, I would have gotten into that. There’s clearly a difference between capillary blood glucose and interstitial glucose, and likely that is magnified in exercise. We can say there is a difference but not necessarily an “error,” but that’s the terminology typically used when comparing sensor data and CBG data.

Q: Did you do try time shifting the data?

A: We did. We did not see any significant delay, so that did not impact the accuracy by time shifting.

Q: Did it matter if the glucose was high or normal coming into exercise?

A: We didn’t look specifically at that, but we’re preparing the publication. We looked at tertiles of drop in glucose and saw that there was a tendency to have higher MARD at the highest tertile.

9. WaveForm CTO Dr. Rebec Continues to Tout Promising Cascade CGM Data; No Updates on Device Launch (>1 Year Behind Schedule)

CTO of WaveForm Technologies Dr. Mihailo Rebec introduced data for the Cascade CGM device that recently obtained a CE mark and is being launched in partnership with distributor A. Menarini. The device consists of a sensor placed on the abdomen, using a needle-free inserter. The transmitter contains all the processing electronics and appears to be higher off the body compared to the Dexcom G6. An attractive, color-coded app is available, which features predictive alarms. The system requires one calibration per day. Dr. Rebec presented extensive accuracy data. In the device’s pivotal trial (n=57 participants, n=108 sensors), overall MARD was 11.1% compared to YSI, with 99.3% of points in the A and B regions on the Clarke Error Grid. Prior tests had established comparable MARD to the Dexcom G5 and Abbott’s Freestyle Libre. Dr. Rebec also noted that the system has the lowest ecological impact of any commercial CGM system, but no specifics were provided. As of November 2019, the Cascade CGM system was set to launch in Europe, however, we have not heard any updates as of yet (putting launch more than one year behind schedule). Stateside, the company plans to file a 510(k) with the FDA as an iCGM “in 2020” with a US launch “in 2021.”

  • WaveForm has partnered with A. Menarini to distribute the Cascade CGM/GlucoMen Day CGM System. The system consists of an insertion device, the sensor and a phone app. The intention is to provide a CGM device with comparable accuracy to the competition, but also a superior user experience, minimal interference (e.g., acetaminophen) and the lowest ecological impact.

  • The sensor insertion is reported to be less painful than a fingerstick by 70% of participants in a study. Pain was recorded using the Gracely pain scale. The insertion device doesn’t use a guide needle because the sensor is a wire filament and it can pierce the skin. A skin reaction analysis showed a low reaction to the system.

  • 21 potential interferents were tested and cleared, including ascorbic acid, acetaminophen, fructose, lactose, caffeine and metformin. At all therapeutic levels, the sensor bias was within limits for both high and low glucose readings.

10. Dr. Bruce Bode Presents Sneak Peak Data of URLi vs. Humalog in MiniMed 670G: No Major Differences in Glucose Profiles; Full Results at ADA 2020

In a talk reviewing ultra fast-acting insulins in closed loop systems, Dr. Bruce Bode (Emory University) presented results from a randomized, double-blind, outpatient, crossover, active-controlled trial of URLi vs. Humalog in type 1s on MiniMed 670G. Dr. Bode is a lead investigator of the trial, and presented results from the patients (n=36) at his study site; full results including patient data at the other site in the trial will be presented at ADA 2020. Looking at ambulatory glucose profile (AGP) comparisons between the two groups and lead-in data where all patients were on Humalog, data look very similar (see slides below). Dr. Bode noted that glucose levels appear to be lower during breakfast, higher during lunch, and about the same for dinner when comparing URLi to Humalog groups. There were no differences in hypoglycemia, and Dr. Bode stressed that Time in Range figures showed that both groups overall only spent 0.7% time in hypoglycemia, which is especially “unheard of” considering the low A1c’s the patients in this trial were at (baseline 7%, baseline Time in Range 78%!). Regarding why the faster acting URLi did not convey more noticeable benefits in terms of improving glucose profiles, we imagine that changes must be incorporated into closed loop algorithms to fully incorporate the improved PK/PD profiles of these insulins – Dr. Bode briefly touched on this point in terms of why data for this class have been relatively underwhelming in closed loop systems so far. 

11. 14-Week Type 2 Trial of Valeritas’ V-Go Patch Pump Shows No Significant Differences in A1c or Hypoglycemia w/ Regular Human Insulin vs. Analog Insulin

Dr. Pablo Mora (Dallas Diabetes Research Center), a highly regarded protégé of Dr. Julio Rosenstock, presented results from a 14-week study of human vs. analog insulin in Valeritas’ V-Go patch pump in type 2 patients, concluding there is no significant difference between the two options on A1c, hypoglycemia, or total daily dose of insulin. CGM was not used in the study, so Time in Range differences could not be evaluated – session chair Dr. Jennifer Sherr brought this very important point up in Q&A, and we’re very curious as to what Time in Range comparisons may look like between the two groups. Dr. Mora concluded that given the intense affordability concerns with rapid acting analog insulin, wearable patch devices such as V-Go may help in minimizing differences between these more expensive insulins and human insulins and therefore ease affordability concerns. We wonder if cost-effectiveness analyses are planned for V-Go usage in these situations, and how impactful such data may be for payers evaluating V-Go. Regarding what may be driving this effect, Dr. Mora posited that V-Go’s ability to provide a continuous infusion of basal insulin can minimize differences in time action profiles between these two classes of rapid acting insulins. He further added that this option could be especially useful in older patient populations with type 2 (>65 years old), and that additional data on this will be presented at upcoming meetings. See table below for a full breakdown of primary and secondary endpoints from the trial in its per-protocol analysis (n=113 patients).

 

Human Insulin

Analog Insulin

A1c (primary endpoint)

-0.60%

-0.38%

Change in hypoglycemia (pre to post number of subjects)

+3

+3

Change in total daily dose of insulin (units/day)

+0.78

+1.82

  • Regarding safety, Dr. Mora emphasized that there were no severe hypoglycemic events in the entire trial.

  • On why CGM was not used in this trial, Dr. Mora pointed to access issues and the question of resource allocation in funding and planning the trial – this is truly disappointing since so much more value and positivity could have been shown. He said that the investigators “debated for six months whether we would use CGM in this trial or for at least a subset of the trial population. But we decided to use CGM eventually in a separate study in a future. We have to remember that this was a relatively older population that has a difficult time in accessing insulin even. Access to CGM in real clinical life is very challenging as well. We look forward to looking further into using CGM in the future trials.” It is worth noting that V-Go has been a type 2 product, a market where CGM access is often much more challenging.

12. Dr. Rich Bergenstal Highlights Accomplishments and Challenges with MiniMed 670G

In one of the most entertaining and informative talks so far at ATTD, Dr. Bergenstal discussed the accomplishments and challenges of the Medtronic MiniMed 670G hybrid closed loop system, now >3 years old. The number one accomplishment was simply that 670G was the first FDA approved AID system. He commented that “[Medtronic] took a dream and turned it into a reality.” Of course, because it was first generation system and expectations were set high, there was an inevitable mismatch with real world experience. While some may have expected 670G to truly automate insulin delivery, 670G still requires work to operate and we have seen a substantial amount of discontinuations. However, Dr. Bergenstal shared testimonials from some users who have been moved to tears by the benefits compared to their old pumps (in a moving video) and many have found that the improved glycemic control more than justify the work required, especially considering that prior systems also had significant associated burdens. Many of the discontinuations of 670G have been due to poor upfront training (see highlight directly above) or the desire to switch to a CGM system that didn’t require fingerstick calibration. Additionally, an analysis by Dr. Boris Kovatchev (University of Virginia) showed that adjusted results from the pivotal trials of the 670G and the Tandem Control-IQ were comparable in Time in Range (72% versus 74%) when adjusted for cohorts and time in “active treatment” (i.e., closed loop). Indeed, for most, the challenge with using MiniMed 670G is simply staying in Auto Mode. Dr. Bergenstal chose to conclude with a key point – that we should be working towards the day when AID is the de facto standard of care.

  • In a video, we saw some compelling testimonials for the 670G from users:I wake up in the morning and it’s almost always 90-something or 100-something (mg/dl). Makes you feel like it adds years to your life.”

  • A 12-month real-world study showed that 33% (26 out of 79) of 670G users stopped using Auto Mode. The Guardian Sensor 3 is considered the greatest challenge to using 670G – Dexcom G6 and Abbott FreeStyle Libre, in particular, have longer wear time, factory calibration, and non-adjunctive labeling. Discontinuation of 670G is predicated on too many calibrations, frequent alarms and too much time needed to make the system work. In children users, “difficult to calibrate” and “too many fingersticks” were the top two reasons for discontinuation cited by parents. On the other hand, higher levels of up-front training have been associated with far fewer discontinuations.

  • A meta-analysis of the pivotal trial results for the 670G and Tandem Control IQ showed comparable TIR results, after adjusting for baseline differences. The analysis performed by Dr. Boris Kovatchev and Dr. Marc Breton from University of Virginia concluded that Control-IQ demonstrated 74% Time in Range compared to 72% for the 670G, after adjustments (see photo). In another key difference, Control-IQ’s pivotal showed 92% time in closed loop, while 670G’s time in closed loop was lower (87%). In real-world data, 

  • In a later talk in the same session, the legendary Dr. Barnard-Kelly (University of Southampton) drove home the point that the closed loop is still burdensome for people with diabetes, but if we support them, we can get great results. Different people need different onboarding and expectations should be managed up front. But in a psychological study of adolescents on closed loop and their parents, participants felt less burdened, had better glucose control, and reduced worry. She noted “All the things people are hoping for, they are getting from these systems. It would be really a shame for all the chatter to detract from the fact that they are successful and getting better.”

  • Amy Winscombe gave her personal perspective on living with MiniMed 670G. She noted it has turned out to be excellent overnight and she wakes up at 100 mg/dl every day. She doesn’t worry about her glucose levels because they are always in range or heading there. The major negative for her is having to wear a CGM, which makes her feel self-conscious. Ms. Winscombe also noted her improved headspace from reduced diabetes burden. She felt that she had “got something always looking out for me.” Additionally, her family is a lot less anxious and “we all feel that I am safer.” “I rarely have hypos now, or I go low but not as low as I would have done before. I feel I am more likely to have a long, healthy, happy life.”

Selected Questions and Answers

Q: Did pre-existing DIY systems put the bar too high?

A: I have the highest respect for the genius of the DIY folks. It worked for them, but commercializing it and getting [the 670G] through the FDA… was “safety, safety, safety, safety”. If you have one DKA or severe hypoglycemia in your trial, it will stop tomorrow. So I think the [670G] algorithm was designed to be a little bit conservative. So maybe the DIY people saw a difference, because they were already on to generation two.

Q: Should the 670 G be given to everybody, or in reality would you argue for the selection of patients?

A: Well, you start off with a new product and there are exclusions. For example, no hypoglycemia. For the next generation trials we are taking MDI patients, hypoglycemia unawareness, people who have never used a sensor etc. The first participants were people we had confidence would get through the trial. But now we feel better because AID lowers hypoglycemia quite significantly. So hypoglycemia unaware folks would be perfect candidates.

Q: Why didn’t Medtronic release a product to automatically handle the correction bolus?

A: Everyone wants this, but the product is first generation. There was a limit to what could be done in the first round. The whole notion of autobolus came to be by observation. We will see if the next system is any better at ADA in June. You only learn by doing. For example, we’ve learned that you should be able to drop the set point from 120 to 100. That’s possible, it’s now being tested.

Q: When will we get to 100% Time in Range?

A: I’ll be watching that from the rocking chair. But I will be around when we get to 80% for sure.

13. Dr. Charlotte Boughton on AID Systems: Users Still Need to Know the Fundamentals of Diabetes Management, AID Should be Available for All Populations

Dr. Boughton, who takes the view that everyone can benefit from closed loop, gave a comprehensive talk that was clearly informed by her deep insight into people with diabetes. Covering a lot of ground, she first noted that we are still living in a world of hybrid closed loop therapy, requiring interaction from the user. She emphasized the need for closed loop users to still “get the basics right,” including carb counting, infusion set changes, eating low glycemic index foods, timing the bolus properly, and not over-bolusing (since the algorithm can fill in for any under-dosing). She then reviewed AID work with various patient segments – very young children, adolescents, the elderly, pregnant women, and those with hypoglycemia unawareness. Broadly, she concluded that regardless of the segment, studies show a clear benefit, and that there are always some people in each group who are going to get great results on closed loop. Healthcare providers often have prejudicial assumptions about which people will or won’t do well on closed loop, but these assumptions are often incorrect and should therefore be avoided –for example, facility with technology is not a requirement for success. Since all segments can benefit from AID, Dr. Boughton concluded by asserting that reimbursement should be available for everyone.

  • Other important “basics” of diabetes management include – insulin bolus timing (avoiding post-meal bolusing which can lead to hypoglycemia), preventing insulin stacking, preventing hypos (by looking to see what insulin has been given and using longer acting carbs), and suspending insulin delivery if the pump is unattached.

  • The CARES paradigm, developed at Barbara Davis Center, is a useful, standardized approach for understanding a closed loop system. CARES stands for Calculate, Adjust, Revert, Educate, Sensor/Share. Translated, this means “how does the algorithm work?,” “what can the user do to influence insulin delivery?,” “when does the system revert to open-loop?,” “what training is required?,” and “how does the CGM work and how is data shared and monitored?.”

  • Dr. Boughton reviewed the literature on closed loop in various segments of the diabetes population. She stated “pretty much everybody will gain benefits from closed loop therapy.” She showed:

    • In very young children (2-6 years), closed loop improved time in target from 55% to 73%. They have greater insulin variability especially overnight. Parents spend less time worrying and more time sleeping.

    • Adolescents with poor control (average age 14 years) improved Time in Range from 48% to 67% - a “massive improvement.” MiniMed 670G and Tandem Control-IQ both show benefits in this cohort.

    • In the Tandem Control-IQ pivotal trial, participants with A1c >7.5% improved time in target from 51% to 64% while also improving hypoglycemia.

    • Older adults were able to benefit from closed loop, despite a high burden of hypoglycemia at baseline, being naïve to sensors, and having more visual impairment.

    • There is currently a trial recruiting for those with hypoglycemia unawareness.

    • In pregnant women, (in the delightfully named PICLS trial) closed loop improved time in target from 60% to 75%. Hypoglycemia was unchanged.

Diabetes Therapy, NASH, and Big Picture Highlights

1. Dr. Jay Skyler Provides Sweeping Overview of Type 1 Cures Landscape w/ Particular Focus on Beta Cell Replacement Efforts

In the final talk of ATTD 2020, Dr. Jay Skyler (University of Miami) looked toward the future of the type 1 cures landscape, with a particular focus on beta cell replacement efforts. Dr. Skyler’s sweeping overview of the field was relatively optimistic and reviewed the many potential strategies toward functional cures that are being studied. Broadly speaking, we’ve noted renewed investment and work in this area of beta cell replacement and type 1 cures in recent years (see Reflections from 2018 and 2019), and commend Dr. Skyler for bookending this meeting by highlighting these advances and pointing toward a hopeful future.

  • Dr. Skyler mentioned several private and public sector initiatives in beta cell replacement efforts, highlighting ongoing work at Orgenesis, ViaCyte, Semma, Novo Nordisk, Lilly, and others.  He noted that scientific advances have allowed the application of stem cell technology to drive forward most progress in the beta cell replacement field, and touched on the diverse strategies that stakeholders can choose to push forward in this space (patient specific stem cells, human embryonic stem cells [hESC], or induced pluripotent stem cells [iPSC]). Regarding the relative benefits/drawbacks of each of these approaches, Dr. Skyler explained that with an autologous (patient specific) stem cell approach, immune rejection can be avoided – a huge plus in ensuring that patients would not need to be under chronic immunosuppression therapy. On the other hand, the process is not as scalable, given that biopsies are needed of each individual patient, and specific manufacturing processes are needed for each individual. With allogenic stem cells (either hESC or iPSC), the process is “generic” in the sense that the same cells could be used for multiple patients. The process is also centralized in a more controlled setting, leading to a more scalable and translatable process for commercialization. ViaCyte and Semma are both pursuing this strategy, while Orogenesis is using the autologous route (see bullet below).

  • We were glad to hear Dr. Skyler give a small update on progress at Orogenesis, as we haven’t heard much on this project in recent years. Dr. Skyler noted that the company is “on the verge of beginning human clinical trials” and that this will happen in 2020 or 2021. Orogenesis was mentioned in relation to it being the only company to conduct autologous stem cell research (patient specific stem cells, coming from the same host), which is a multi-step process that requires the modification of multiple cellular processes. The idea here is to revert liver cells to a suggestible stem-cell state, induce pancreatic differentiation, then fine tune the signaling pathway to allow generation of cells which secrete insulin – certainly no small feat. Dr. Skyler commented that preclinical work from Orogenesis has shown that differentiated cells show “total physiologic insulin response to glucose and the production of C-peptide” – a fantastic signal as the approach moves into clinical work.

2. Buzzing NAFLD/NASH Session Highlights the Strongest Drugs in the Competitive Landscape, Epidemiology, and Machine Learning Approaches for Improved Diagnosis

A morning session on the NAFLD/NASH therapy landscape drew a standing-room-only crowd (impressive for a Saturday morning, and at a tech conference no less!). The highlight was Dr. Cristophe de Block’s (Antwerp University Hospital, Belgium) tour de force of the ever-growing landscape of therapies in development for NAFLD/NASH. In a very helpful synthesis, he segmented the many drug classes into those that target insulin resistance, inflammation, lipid metabolism, and fibrosis, as shown below.

Anti-insulin resistance

  • TZDs

  • GLP-1 agonists

  • GLP-1/GIP dual agonists

  • SGLT-2 inhibitors

Anti-inflammatory

  • Vitamin E

  • Dual PPAR α/δ agonists

Lipid metabolism correcting

  • FXR agonists

  • SCD-1 inhibitors

Anti-fibrotic

  • CCR2/CCR5 antagonist

  • Thyroid receptor β agonists

  • FGF-21 analogs

Within these, Dr. de Block expressed particular optimism for the generic TZD pioglitazone, Lilly’s GLP-1/GIP dual agonist tirzepatide, and Intercept’s FXR agonist obeticholic acid (now under priority review with the FDA), but also underscored that “the first line of treatment is a lifestyle approach, the second line of treatment is a lifestyle approach, and the third line of treatment is a lifestyle approach” given the tight association between NAFLD/NASH and diabetes and obesity (just 7% weight loss will halt the worsening of fibrosis and >10% weight loss leads to resolution of NASH and regression of fibrosis), and the fact that so many of these agents in the NAFLD/NASH competitive landscape have yet to undergo larger and longer-scale trials. In particular, he outlined that the cornerstones of any NAFLD/NASH treatment plan (regardless of which drugs are eventually approved) should be caloric restriction, reduced fructose intake, reduced daily alcohol intake, and increased physical activity.

  • Nodding to the mixed clinical trial results, hepatologist Dr. Zobair Younossi (Inova Fairfax Hospital, Falls Church, VA) pointed out the difficulty in clinical trial design for a disease whose natural history involves progression and regression between the increasingly severe stages of steatosis, fibrosis, and cirrhosis. Dr. Younossi explained that having 10% of a population spontaneously revert to a less advanced phase of NAFLD/NASH is not unusual, but the occurrence of this in the placebo arm of a trial can muddy the interpretation of the results. Additionally, NAFLD/NASH candidate therapies have a different impact on the steatosis, fibrosis, and cirrhosis given the different pathophysiological mechanisms underlying each stage of the disease. This infinitely complicates clinical trial design and raises challenging questions about patient selection and segmentation.

  • Dr. Younossi also provided a deep dive on the epidemiology and burden of NAFLD/NASH. In lockstep with the global obesity and diabetes epidemic, NAFLD/NASH is on the rise, currently affecting a staggering ~25% of the global adult population, and ~50-60% of the global type 2 diabetes population. In the US alone, it is estimated that 6.65 million adults have NASH, and within this nearly 700,000 have the most severe advanced fibrosis. Particularly concerning, Dr. Younossi pointed to the rise of this condition in children as an “emerging tsunami.” Currently NAFLD affects ~5-7% of children in North America, Europe, Asia, and Africa, and as high as ~25% in South America. Overall the global lifetime cost of NASH for the entire patient population is estimated at $222 billion, and no doubt this will only rise as liver disease strikes younger patient populations.

  • In a discussion of NASH diagnostics, University of Colorado’s Dr. Kavida Garg highlighted the growing interest in using computational and machine learning approaches to detect liver steatosis and fibrosis from MRI images. Currently the gold standard for NASH diagnosis is liver biopsy – a costly and invasive procedure that is not scalable at the population level. Machine learning analysis on top of the MRI imaging that is already performed in NAFLD/NASH patients could be game-changing for detecting liver disease earlier, and screening more widely. As Dr. Garg put it, “images are more than pictures – they have a lot of data.” We’ll be following this closely.

3. Dr. Simon Heller on Cognitive Consequences of Hypoglycemia

Dr. Simon Heller (University of Sheffield, UK) gave a fascinating overview of the cognitive consequences of hypoglycemia, and the potential of CGM to help prevent this. He underscored that in addition to short-term concerns such as transient cognitive dysfunction, confusion, and behavior abnormalities, hypoglycemia is also associated with long-term risk of cognitive impairment and possibly even dementia. Results from the longitudinal Edinburgh Type 2 Diabetes Study show that the frequency of severe hypoglycemia is negatively associated with cognitive ability, and a recent meta-analysis demonstrated that use of insulin, with its accompanying hypoglycemia risk, increases the risk of dementia by approximately 50%  (pooled HR: 1.54, 95% CI = 1.14-2.007). Turning to younger patients, data from a Norwegian population study demonstrated that children with type 1 diabetes who had experienced severe hypoglycemia before the age of 10 had worse cognitive function after 16 years of follow-up; the effects were most damaging for children who experienced severe hypoglycemia before the age of 6. Though these findings are extremely concerning, Dr. Heller ended the talk on an optimistic note. Greater use of CGM can help people detect hypoglycemia events they were previously unaware of based on symptoms alone. This raises the possibility of identifying new risk factors for hypoglycemia, predicting risk of severe hypoglycemia episodes, more precisely measuring the impact of symptomatic and asymptomatic hypoglycemia on cognitive function, and – very crucially – greater precision in measuring the effectiveness of new diabetes therapies and technologies designed to reduce the risk of hypoglycemia.

4. Enthusiasm Builds for Nasal and Injectable Next-Gen Glucagon Hypoglycemia Rescue Treatments

Back-to-back talks from Yale’s Drs. Jennifer Sherr and Stuart Weinzimer highlighted recent advances in glucagon rescue therapy for severe hypoglycemia, both subcutaneous and nasal. Dr. Sherr highlighted Lilly’s nasal glucagon Baqsimi, FDA approved in July 2019 as the first-ever non-injectable rescue treatment for hypoglycemia. She emphasized that nasal glucagon represents an enormous innovation for the field. Current glucagon reconstitution kits are cumbersome, time-consuming, and error-prone, as they require mixing and injecting steps that often cannot be performed by the individual experiencing the hypoglycemic event. On the other hand, Baqsimi will come in a single-use dispenser that can directly administer nasal powder glucagon without the need for preparation or injection. To this end, Dr. Sherr highlighted the human factors study for Baqsimi, in which 6x as many caregivers correctly gave a full dose of nasal glucagon in 8x less time. It’s safe to say that people with diabetes who at risk for severe hypoglycemia have been waiting for an alternative for quite some time, and Dr. Sherr underscored that this therapy also comes as a giant sigh of relief for their families and care partners. The highlight of the presentation, in our view, was Dr. Sherr’s demonstration of how to use Baqsimi – as a person with type 1 diabetes herself, she keeps a vial with her in her purse. We were also pleased to hear Dr. Sherr highlight our very own Ms. Kelly Close’s testimonial about her personal experience with Baqsimi, available here at diaTribe Learn.

  • Turning to liquid-stable glucagon preparations, Dr. Weinzimer underscored the game-changing convenience of these vs. cumbersome reconstitution kits. Xeris’ GVOKE glucagon injection was FDA approved as the first treatment of this kind in September 2019; launch is expected later this year in the forms of a pen and a pre-filled syringe. Other liquid-stable glucagons in the pipeline include Zealand’s phase 3 HypoPal rescue pen (dasiglucagon) and Adocia’s phase 1/2 Bio-Chaperone glucagon. Another application of liquid-stable glucagon is use in dual hormone AP systems, and to this end Dr. Weinzimer highlighted BetaBionics’ iLet bionic pancreas, which includes dasiglucagon alongside insulin. BetaBionics recently unveiled strong phase 2 results from the dual hormone AP’s first-ever home-use outpatient trial (90% of dual-hormone iLet users had a mean CGM glucose level <154 mg/dl, vs. 50% with the iLet running on insulin only). A phase 3 trial is slated to begin later this year.

5. Social Media Session Touches on #LanguageMatters, Pros and Cons of Social Media, and Digital Peer Support

A lively session on social media addressed the pros and cons of online platforms and the growing #LanguageMatters movement. The session was headlined by the dynamic duo of Renza Scibilia and Chris “The Grumpy Pumper” Aldred, two fantastic type 1 diabetes advocates who discussed the #LanguageMatters movement and how HCPs can interact with their patients in a more understanding and empathetic way. The centerpiece of the conversation was a recent viral Twitter thread in which an ophthalmologist advocated for giving people with diabetes a “wake up call” about retinopathy by threatening them with pictures of diseased retinas. Ms. Scibilia and Mr. Aldred both emphasized that the use of such “shock tactics” work for very few people with diabetes. In most cases, it will cause patients to tune out, or worse, paralyze them into inactivity. Ms. Scibilia underscored that “we know how serious diabetes is – we’re living with this in our bodies every day.” She advocated changing the conversation to “care, rather than complications” – what people with diabetes need is an action plan, not another reminder of the burdens of diabetes. Mr. Aldred, who was recently diagnosed with a foot ulcer, his first diabetes complication, underscored that stigma about complications is a giant weight on the shoulders of people with diabetes. He told the story of telling his podiatrist how crushed he felt when she called him “non-compliant” – thankfully, his podiatrist has now vowed to never use that term again. He gave the following advice to HCPs in the audience: “In an appointment, your first question should be ‘how are you, and how’s your family?’ because what influences this will influence your diabetes.”

  • NHS England’s Dr. Partha Kar followed with a discussion of the pros and cons of social media, drawing upon his own recent negative experience on Twitter involving a harsh backlash against his post picturing a weekend pancake breakfast (to the tune of “how dare you as a diabetes leader eat unhealthy food?!”). Despite the negativity and divisiveness that social media can bring, Dr. Kar said that he still uses it first and foremost because it is a fantastic platform for education, information gathering, and interacting with colleagues and people with diabetes. Alluding to recent game-changing advances in diabetes therapy and technology, Dr. Kar expressed concern that these advances so far have favored only the few, improving life for people who already have ample resources to manage their diabetes, and leaving those without even further behind. He argued that social media can be a democratizing force in this regard, spreading peer support and self-management tips more broadly in the population.

  • University of South Hampton’s Dr. Claire Reidy underscored the benefits and pitfalls of structured peer support and its importance in diabetes self-management. Some benefits include shared learning (as people spend more time engaging in self-management than working with an HCP), online sources of support that allows people to access and address issues, and improved feelings of self-efficacy and group belonging. Potential pitfalls include a lack of accountability and credibility, no clear guidelines, potential judgement from peers, and misinformation. Dr. Reidy remained optimistic that structured peer support in the form of blogs, forums, and more can indeed be an important “lifeline” that provides emotional support in addition to traditional clinical outcomes.

  • Dr. Neal Kaufman (CMO of Canary Health) tackled an interesting topic: the use of “Digital Therapeutics” for people with diabetes. Digital Therapeutics (DTx) are a form of digital peer support communities, and can be an important means of delivering therapeutic interventions to patients directly. As an example, Dr. Kaufman cited “Better Choices, Better Health,” a six-week, digital peer-to-peer workshop that provides tailored education and action planning to a group of 25-30 participants at a time. The workshop not only increased self-efficacy among its participants, but also improved their confidence to adopt health behavior change. According to Dr. Kaufman, best practices for online digital support include increasing self-efficacy as a primary outcome, tailoring content that enables community discussions, and including skilled peer coaching. In Q&A, when asked about how physicians can assist in improving self-efficacy, Dr. Kaufman responded that doctors must ask these three questions to their patients: (i) What do you think is wrong?; (ii) What at do you think is causing it?; and (iii) How can I be of help?

 

--by Sahaj Shah, Abigail Dove, John Close, Ani Gururaj, Martin Kurian, Rhea Teng, Albert Cai, and Kelly Close