ATTD (Advanced Technologies and Treatments in Diabetes) 2020

February 19-22, 2020; Madrid, Spain; Day #1 Highlights - Draft

Executive Highlights

  • Abbott hosted a very comprehensive corporate symposium this afternoon, hosted by the widely respected (many would say, even, cherished) Dr. Tadej Battelino. Dr. Battelino grabbed the attention of the audience early on when he instructed them to put DCTT in the “history drawer part” of their brains. He was specifically referring to the DCCT finding that rates of severe hypoglycemia increase with more favorable (lower) A1c. Based on results of multiple CGM studies, Dr. Battelino argued that it is now possible to achieve low A1cs without increasing rates of severe hypo. Dr. Ramzi Ajjan (University of Leeds) showed convincing real-world data from thousands of FreeStyle Libre users, showing that time spent in hyper- and hypoglycemia tended to decrease with increased scanning frequency. Broken down by country and region, there were some notable variations that we’d love to see more detail on in the future – we’d also love to get researcher views on the sources of the differences.

    • Also at the Abbott symposium, Dr. Rich Bergenstal (International Diabetes Center) held the audience at rapt attention as he shared a few of his many catchphrases (Rich-isms?) for interpreting CGM data. Among the three that he shared, MGLR (more green, less red; refers to the stacked Time in Range bars), “thinking fast and slow” (refers to making “fast” in-the-moment therapeutic or behavioral changes based on real-time CGM numbers or trends and “slow” deliberative analyses of AGPs – many also know the famous and Nobel-prizewinning book by this name), and FNIR (Flat, Narrow, In-Range), FNIR was the biggest hit as many providers pulled out their camera-phones to snap a picture of Dr. Bergenstal’s slide. We’ve also heard of the aspirational STAR – Steady, Tight And in Range!

  • At a Medtronic-sponsored symposium, we got a look at cost-savings data from the single-arm Portuguese ADJUST study (n=102 type 2s) of the iPro 2 professional CGM. When comparing the study cohort to a hypothetical cohort who did not receive the blinded CGM treatment, Medtronic found that the blinded CGM resulted in an incremental cost-effectiveness ratio of €6,767 /QALY (~$7,304), an increase in quality-adjusted-life-years (QALYs) from 8.49 to 8.58, and reduced the costs of complications from €68,699 (~$74,150) to €68,084 (~$73,486). To put some perspective on these numbers, Dr. Portu mentioned that the Portuguese government is willing to pay for a medical intervention if it demonstrates an ICER of €50,000/QALY. This amounts to a roughly seven-fold cost differential that blinded CGM can provide for the same impact!

  • Now in its 13th year, ATTD was kicked off Wednesday evening at an opening ceremony hosted by conference co-chairs Profs. Moshe Philips and Tadej Battelino with a keynote presentation by Dr. Jay Skyler (University of Miami). This year’s meeting features over 3,800 participants from more than 81 countries. In total, 615 abstracts were submitted, and the conference will feature 26 scientific sessions, 10 oral sessions, and 14 industry symposia – if that’s overwhelming, see our preview for some of the sessions to which we’re most looking forward.

Hello from Madrid, Spain, where ATTD 2020 officially kicked off this evening! See our top highlights from the day from corporate symposia hosted by Abbott and Medtronic and the opening ceremony.

Top Five Highlights

1. Dr. Tadej Battelino: Put DCCT in the “History Drawer” Of Your Brain, Lowering A1c No Longer Requires More Hypos; Real-World Data Shows Hypo Exposure Decreases with FreeStyle Libre Scans/Day Across Regions

At Wednesday afternoon’s Abbott-sponsored symposium, Dr. Tadej Battelino (Ljubljana University) told the audience to put DCCT in the “history drawer part” of their brains. To start out his presentation, Dr. Battelino emphasized the detrimental effects of hyperglycemia, in fact using data from DCCT to tie higher rates of complications (e.g., cardiovascular disease, cognitive impairment) with higher A1cs. On the other hand, Dr. Battelino presented data showing non-severe hypoglycemia was protective against cognitive dysfunction, while severe hypoglycemia had no significant effect. Thus, Dr. Battelino summarized the challenge of managing diabetes: lower A1c (i.e., reduce hyperglycemia) while avoiding severe hypoglycemia. Then, Dr. Battelino caught the audience off guard, telling them to put DCCT in the “history drawer part” of their brains. Dr. Battelino was specifically referring to the DCCT finding that rates of severe hypoglycemia increase with decreasing A1c. In a telling graph (see below), Dr. Battelino overlaid data from multiple CGM studies with the same DCCT graph showing a rapid increase in severe hypoglycemia rates as A1c decreased. The CGM study results (circled below) showed no differences in severe hypo rates, whether A1c was above or below 7%. Additionally, the rates of hypoglycemia were markedly lower in the CGM studies compared to DCCT. Given the setting of an Abbott-sponsored symposium and Dr. Battelino’s focus on severe hypoglycemia, we were somewhat surprised we didn’t hear any mention of Abbott’s FreeStyle Libre 2, which adds optional high and low alarms in the same form factor as the original FreeStyle Libre.

 

  • During his talk at the symposium, Dr. Ramzi Ajjan (University of Leeds) presented real-world data showing that increased FreeStyle Libre scanning frequency was associated with reduced time in both hyperglycemia and hypoglycemia across many countries and regions. The first set of graphs, taken from Dunn et al., 2018, show this same pattern in five European countries. Of course, there are some interesting differences in the different countries’ time spent in hyper- and hypoglycemia – we’d be curious what sorts of cultural, social, and environmentally-driven factors could be driving these variations. Overall, and fascinatingly, the number of minutes per day in hypoglcyemia had very little variability in some countries such as Germany; Italy had the least “time in hypoglycemia” when patients scanned up to 40 times a day at 18 minutes per day – other countries where patients scanned at that rate had a much higher “time in hypoglcyemia” such as France at 40 minutes. For patients who scanned closer to five times a day, time in hypoglcyemia was as high as 57 and 59 minutes a day in Spain and France and as low as 34 and 36 minute a day in Germany and Italy! On the “time in hyperglycemia” side, all patients in all countries shown had between 9.5 and 10.7 hours per day in hyperglycemia if the scans were around five per day – that is between 40% and 45% “time in hyperglycemia” – however that fell to 5.8 to 7.1 hours a day in hyperglycemia or between 24% and 29% “time in hyperglycemia – a massive difference! The most “learning” was in the UK, where the lowest number of scans (~five/day) yielded 44% time in hyperglycemia, which fell to 24% time in hyperglycemia with the higher number of scans – wow! Half-jokingly, Dr. Ajjan suggested that Italy’s relatively low percentages of time spent in hypoglycemia at 1.2% at the low end to 2.3% at the high end were due to pasta – this made us wonder on average how many carbs per day are consumed per country and where the biggest and smallest standard deviations are. “Time in hypo” was higher for other countries, coming in at a range between 1.8% at the low end and 4.1% at the high end for the other countires. Interestingly, Dr. Ajjan also compared the European data to countries in other regions: real-world FreeStyle Libre data from Brazil showed similarly reduced A1c as scanning frequency increased; however, the relationship between hypoglycemia and scanning frequency was much less clear. Lastly, Dr. Ajjan showed unpublished data (picture not shown) from the Middle East, highlighting a marked decrease in both A1c and hypoglycemia as scanning frequency increased – we’d love to see average numbers for those countries as well, in order to think more specifically about regional interventions.

  • Dr. Ajjan also presented real-world data from FreeStyle Libre showing that reductions in hypoglycemia appeared after just one day, while the improvements in hyperglycemia took closer to two months on average to appear. Dr. Ajjan hypothesized that this delay in observed hyperglycemia reduction was because patients needed to review their data in clinics with providers to help identify behaviors that might be causing hyperglycemia; this seems logical to us since they can more immediately avoid hypoglcyemia by identifying it and taking in carbs, etc. – the power of data!

2. ADJUST Type 2 Professional CGM Study Scores Cost-Effectiveness of €6,767/QALY (~$7,304); Potential Long-Term Savings of ~€5,000 (~$5,397) and Complication Onset Delay by One Year

Medtronic’s Dr. Simona de Portu presented some of the first cost-effectiveness data from the single-arm Portuguese ADJUST study of the iPro 2 professional (blinded) CGM, highlighting that blinded CGM could reduce costs for patients, over the long-run, by ~€5,000 (~$5,397) due to avoided diabetes-related complications, along with delaying the onset of complications by roughly one year. Medtronic used healthcare consulting company IQVIA’s Core Diabetes Model, an increasingly popular health-economics simulation model, to compare the cohort of patients that received blinded CGM to a hypothetical cohort of patients that did not receive it. The model assumed that patients who received iPro 2 had three blinded CGM visits per year and that that patients who did not receive the professional CGM maintained a flat A1c and visited a doctor four times per year. The model also took into account the costs of the insertion/ review of the data after one week for patients who received the blinded CGM. When comparing the two cohorts, Medtronic found that the blinded CGM resulted in an incremental cost-effectiveness ratio of €6,767 /QALY (~$7,304), an increase in quality-adjusted-life-years (QALYs) from 8.49 to 8.58, and reduced the costs of complications from €68,699 (~$74,150) to €68,084 (~$73,486). To put some perspective on these numbers, Dr. Portu mentioned that the Portuguese government is willing to pay for a medical intervention if it demonstrates an ICER of €50,000/QALY. This amounts to a roughly seven-fold cost differential that blinded CGM can provide for the same impact! Even more impressively, these findings stayed constant when the time horizon of the analysis changed by five, ten, or twenty years, when the assumed cost of complications was increased or decreased by 20%, or when the discount rate was altered. These findings illustrate that despite the increased administrative costs that result from visiting HCPs, purchasing a blinded CGM, and inserting/removing the device, these costs were partially offset by a meaningful reduction in complications and improvements in quality of life.

  • As a reminder, the ADJUST study (n=102 type 2 patients) found that at 12 months, following quarterly CGM applications, each with a follow-up visit (in-person or by phone), A1c levels had dropped by a mean 1.3% (baseline: 9.4%), mean glucose had dropped from 185 to 170 mg/dl, and percent time above 180 mg/dl decreased from 48% to 37% without any increase in time spent in hypoglycemia. Beyond improved glycemic management, patients reported increased treatment satisfaction and better communication with their healthcare providers. From a therapeutic standpoint, patients using blinded CGM were also able to focus their treatment regimens to either pharmacological or behavior modifications after originally using a broad mixture of both adjustments when first starting on the CGM. See our ATTD 2019 report for a deeper dive.  Presumably even more improvements could be made if treatment changes that “worked” best were carefully analyzed – ranging from different therapies to different food choices to different perceived levels of stress.

3. Abbott-Sponsored Symposium: Audience Polls Show Strong Enthusiasm for CGM; Dr. Rich Bergenstal’s “FNIR” (Flat, Narrow, In-Range) is a Big Hit

At the same Abbott-sponsored symposium as above, Dr. Tadej Battelino (University of Lubljana) polled the audience before and after the symposium on several questions related to enthusiasm for and adoption of CGM. The pre-symposium survey revealed that speakers Drs. Tadej Battelino, Rich Bergenstal, and Ramzi Ajjan had a tough job: the audience was already incredibly enthusiastic and knowledgeable about CGM. Before the session started, 64% of the audience rated themselves as either “reasonably knowledgeable and very good level of expertise” or “an expert and extremely knowledgeable” about the “technical aspects and clinical indications” for CGM. Perhaps more impressively, more than half (58%) of the audience said that they “currently recommend and/or prescribe” CGM to >60% of their patients with type 1 diabetes – we’d love to know how many of those recommendations/ prescriptions are actually turned into CGM users. By the end of the session, a larger majority (71%) of the audience said they were likely to recommend and/or prescribe CGM to their type 1 patients. Not surprisingly, the numbers were a bit weaker for insulin-using type 2s at the high end, though the differences in “average opinion” of this group was huge: specifically, 23% of the audience said they recommend and/or prescribe CGM to >60% of those patients; this number more than doubled to 57% by the end of the program. A full breakdown of these questions is in the tables below. The impressive audience knowledge is a testament to the incredible momentum seen in CGM over the past decade – in Dexcom’s most recent quarterly call, we got our first update on Dexcom’s user base in over ~two years. Dexcom’s global user base is “approaching 650,000”; combined with Abbott’s two million FreeStyle Libre users, the number of global CGM is well across the 2.5 million mark. At the end of 2018, we estimated ~1.5 million global CGM users and at the end of 2017, we estimated the user base at “just” 0.7-1.0 million.

  • The audience engagement was palpable in the room as Dr. Rich Bergenstal (International Diabetes Center) gave some tips for interpreting CGM data. The audience responded incredibly enthusiastically when Dr. Bergenstal explained his “FNIR” (Flat, Narrow, In-Range) mnemonic for an ideal ambulatory glucose profile – at least half of the clinicians in the room pulled out their phones to snap a picture of Dr. Bergenstal’s slide explaining FNIR. This has also been very popular among patients in the US who have seen it at diaTribe Learn. A couple more of Dr. Bergenstal’s catchphrases (Rich-isms?) also made their way into the presentation:

    • MGLR: More Green, Less Red; refers to the stacked Time in Range bars; and

    • “Thinking fast and slow” – this refers to making “fast” in-the-moment therapeutic or behavioral changes based on real-time CGM numbers or trends and “slow” deliberative analyses of AGPs (many may also know the famous and Nobel-prizewinning book by this name).

    • STAR: this is another one we’ve heard lately though it wasn’t in the presentation – Steady, Tight And in Range. We’ve loved patient responses to FNIR – very aspirational – and we also love patients thinking about “steadier” glucose levels (it’s hard to achieve flat for many patients though many are working toward it much more readily with CGM mnemonics!).

My current understanding of the technical aspects of and clinical indications for sensor-based CGM in persons with diabetes is:

 

Pre

Post

At an expert and extremely knowledgeable level

26%

26%

At reasonably knowledgeable and very good level of expertise

38%

36%

At an acceptable level of expertise

21%

28%

At a fair level, in need of improvement

8%

8%

At a very fundamental level

8%

2%

Pre-program question - among all persons with type 1 diabetes, the percentage in whom I currently recommend and/or prescribe sensor-based CGM is:

Post-program question – based on my engagement with the content and expert-based presentations provided in this educational program, among all persons with type 1 diabetes, the percentage in whom I am now likely to recommend and/or prescribe sensor-based CGM is:

 

Pre

Post

<5%

8%

4%

5-15%

10%

4%

15-30%

16%

7%

30-60%

10%

14%

>60%

58%

71%

Pre-program question - among all persons with insulin-requiring type 2 diabetes, the percentage in whom I currently recommend and/or prescribe sensor-based CGM is:

Post-program question – based on my engagement with the content and expert-based presentations provided in this educational program, among all persons with insulin-requiring type 2 diabetes, the percentage in whom I am now likely to recommend and/or prescribe sensor-based CGM is:

 

Pre

Post

<5%

23%

3%

5-15%

12%

4%

15-30%

20%

15%

30-60%

21%

20%

>60%

23%

57%

4. Clinical Cases of Envision Pro Highlight Utility of Pattern Snapshot Feature and Ability to Drive Behavior Change

The highly regarded Dr. Fiona Campbell (Leeds Children’s Hospital) highlighted two clinical case studies demonstrating the behavioral modifications that Medtronic’s Envision Pro CGM can enable in CGM-naïve adolescent populations. Dr. Campbell contextualized her talk by addressing the enormous burden healthcare providers face in making clinical data relevant and actionable to patients. We appreciated her candor on this front and acknowledgement of how hard positions are for healthcare providers. As patients also tend to view meeting with their clinicians as the most important component of care (according to Dr. Campbell), using technology such as professional CGM that enables both parties to view data together and to collaborate in shared decision making is critical, stressed Dr. Campbell – we certainly agree if these conversations are well set up and patients can discuss the data on an equal footing to the provider.

In the following examples, Dr. Campbell first provided a description of the patient’s demographics, unique lifestyle needs, and specific difficulty in managing diabetes care. Each patient was then placed on the Envision Pro CGM (CE-Marked at EASD 2019) for approximately one week. During a follow-up visit, Dr. Campbell asked the patient to summarize the data, acknowledge any surprises, and suggest meaningful treatment changes. Dr. Campbell even switched seats with the patient to facilitate the patient’s role as a “teacher” who could then actively identify opportunities for improved care – what a patient-centric approach to care!

Arguably, the most informative feature of utilizing the Envision Pro which Dr. Campbell is its CareLink Pattern Snapshot feature (launched in November 2015), which provides the top three trends identified over the week-long period along with potential causes. The software then provides a number of suggestions: (i) oral medication(s) too high or incorrectly timed?; (ii) basal insulin injection in evening(s) too high or missed?; (iii) pre-breakfast insulin incorrectly timed, incorrect dose, or missed?; (iv) insulin to carbohydrate ratio not optimal for pre-breakfast insulin?; (v) inconsistent food intake?; and (vi) exercise around breakfast time? Wow! Patients can also log food, medication, and physical activity. Dr. Campbell mentioned that these features enabled her patients to pick distinct places in the clutter of blood glucose data where they were struggling with diabetes management and critically think about meaningful changes they could make with respect to medications, lifestyle, and other self-care behaviors. We have heard how popular Carelink is among doctors (with some, perhaps even more popular then the technology) and getting this insider view was very helpful.

  • The first case study related to a 17-year old male patient (A1c 9%, T1 duration 10 years) on insulin pump therapy. The patient was a college student studying for final examinations who was keen on moving away from home and into university. Beyond his high A1c, the patient had background bilateral diabetic retinopathy, well-managed hyperthyroidism (taking 125 daily micrograms of thyroxine), and observed episodes of unexplained hypoglycemia. Interestingly, the patient wanted to stick to pump therapy, but had no desire of initiating CGM. After using Envision Pro CGM for eight days and following up, the patient was able to distinctly identify three key periods of out-of-target glucose ranges with the help of Pattern Snapshot: (i) low values post-dinner from 5:00 PM to 8:00 PM; (ii) high values overnight from 11:00 PM to 6:00 AM; and (iii) high values during fasting times of 5:00 AM to 7:00 AM. By comparing day-to-day glucose profiles, the patient could also begin to compare how blood glucose would vary during periods of relaxation on the weekend, days of intense studying on the weekdays, and periods of exercise. Based on the numbers the patient could now visually interpret, he realized that the consistently high levels of overnight glucose resulted from him eating a large meal at the end of the day because of a job he had at a call center. Because of a desire to avoid nocturnal hypoglycemia, the patient would significantly push glucose levels up before sleeping, not only placing him at risk for DKA but also undoing his work during the day of maintaining optimal glycemic management. With respect to behavior change, the individual became reassured that he wasn’t at risk for hypoglycemia and even considered switching to a real-time CGM. We were struck by “even considered” since we think anyone on insulin should be on real-time CGM and it was presented here as less likely (probably because the person with diabetes may not have wanted to wear real-time CGM).

  • The second case Dr. Campbell presented was from a 14-year old female (A1c ranging from 6%-7%, type 1 duration for seven years) who was using an insulin pump without a CGM because of personal confidence that she knew when her glucose levels were out of range. The individual was an academically high-achieving student who played on her school’s netball team but had become frustrated with erratic glucose values while on SMBG. After using Envision Pro for six days, the patient was shocked during her follow-up to see significant glycemic fluctuations. Furthermore, her Time in Range was just 44%, demonstrating a classic case where A1c does not truly provide an accurate representation of true diabetes management. Her Pattern Snapshot highlighted especially high variations overnight and low sugar levels in the early morning during fasting times. Based on her analysis, the patient was able to recognize that her variations likely resulted from personal behaviors including rushed carb counting, not bolusing before meals, and underdosing insulin prior to bed. She left the discussion with a plan of stabilizing basal insulin on a daily basis, investing sufficient time to carefully count carbohydrates, delivering insulin fifteen minutes before meals, pursuing variable dose ratios throughout the day, and even agreeing to wear real-time CGM. We would love to learn specifically how high her “time in hypoglycemia” was – we are imagining it was well over 10%-15%.

  • While at this point, some conference attendees may feel the benefits of professional CGM are very clear – that they can drive meaningful clinical outcomes, behavioral change and improve treatment satisfaction – we loved this session because it made it clear how many HCPs actually don’t necessarily know the power of professional CGM. Or, at least many HCPs may not have as much as experience using professional CGM as might be assumed. However, driving uptake remains an important issue. On this front, at ADA Postgrad 2020, Cleveland Clinic’s Dr. Diana Isaacs characterized professional CGM as an “underutilized resource” despite “good” reimbursement.” Another key question relates to the benefit the type 2 population can derive from it with respect to when it should be deployed and the frequency of wear. At ATTD 2019, Medtronic’s Dr. Robert Vigersky mentioned that only three to six days of CGM wear time may be needed to obtain actionable information. We believe Professional CGM will become more popular as Dexcom’s G6 Pro approved in October 2019 in the US emerges – it is vastly improved, easier to use, and we believe there will be far more improvements and education on how to best use Professional CGM of all kinds in the future.

5. Opening Ceremony: ATTD Attendance Swells to >3,800 Attendees in 13th Iteration; Dr. Jay Skyler Draws Parallels Between Past and Present in Review of Diabetes Technology

Conference co-chair Prof. Moshe Phillips kicked off this year’s opening ceremony with several stunning statistics on ATTD’s rapid growth. Despite this only being the meeting’s 13th congregation, over 3,800 participants from more than 81 countries are in attendance this year. In total, 615 abstracts were submitted, and the conference will feature 26 scientific sessions, 10 oral sessions, and 14 industry symposia – wow! These statistics were met with enthusiastic clapping, and throughout the day, we’ve chatted with conference goers who all agree that ATTD has quickly become one of the most impactful meetings in all of diabetes, indicative of the powerful momentum behind diabetes technology. (We do point out we were saying this back in 2010 – write us at info@closeconcerns.com if you’d like copies of our “full reports” for ATTD since 2009.) As Prof. Phillips noted, ATTD is particularly focused on innovation and interaction with broad groups of industry and other stakeholders is a mainstay of the meeting – whether that be up-and-coming start-ups or longtime veteran organizations in the field. For those of you who aren’t able to make it to this year’s meeting, we highly recommend you check out the online Education Portal, which will house a selection of the materials being shared. The app is fantastic and will keep you abreast of the sessions that are live-streamed!

  • After a very heart-warming introduction by conference co-chair Prof. Tadej Battelino, University of Miami’s Dr. Jay Skyler took to the stage to deliver a whirlwind, comprehensive, and hit presentation on the evolution of diabetes technology. We were particularly struck by the many parallels Dr. Skyler drew between diabetes care “then” (as far back as the first isolation of insulin in 1922) and diabetes care “now.” For example, Dr. Skyler opened his presentation with a quotation from The Diabetic Life by Dr. Robin Lawrence, first published in 1925, that still resonates today:

The temperament and usual habits of the patient should be considered in the type of treatment chosen and our object should be to interfere with these as little as is compatible with health… I know that full physiological control of severe diabetes – the most continuously normal blood sugar and the least hypoglycemia – can be obtained with 4-6 small injections of soluble insulin in the 24 hours.”

While the means and quality of insulin injection have certainly changed since then, the goals physicians aimed for even 50+ years ago continue to play a role in modern research and care. Similarly, Dr. Skyler highlighted Dr. Ted Danowski’s 1978 Diabetes Care paper “Jet Injection of Insulin During Self-Monitoring of Blood Glucose,” which was the first publication to champion the basal-bolus concept and self-monitoring of blood glucose. As Dr. Skyler put it, “the concepts were all there in 1978.” This framework gave incredible perspective to how far diabetes technology has come in the last 100 years to meet the goals and ideas that have been in discussion for so long. With the advent of closed loop systems, smart insulins, and more, we so look forward to seeing where the field will go in the next 100 years. We highly recommend visiting ATTD’s Facebook page where a video of the presentation is already up!  

  • Closing out the opening ceremony, live Flamenco performance from local Madrid musicians and dancers performed for the crowd. We loved seeing the crowd snap and clap to the music and erupt into cheers after each solo. See below for a photo of the festivities and check out Kelly’s Instagram to see some of the amazing show!

 

--by Ani Gururaj, Rhea Teng, Martin Kurian, Albert Cai, and Kelly Close