June 10-14, 2016; New Orleans, LA; Day #1 Highlights – Draft

Executive Highlights

Hello from New Orleans, where our team has hit the ground running at the Ernest Morial Convention Center, as ADA 2016 has officially kicked off! On the drug side, we got the chance to sit in on the morning’s closed session of the ADA’s powerhouse Pathway to Stop Diabetes grant recipients. We also heard various new data presentations from phase 2 results of combination therapy with AZ’s Farxiga (dapagliflozin) and Bydureon (exenatide once weekly) to positive semaglutide findings in obesity. On the tech front, we bring you tremendous learnings from “Digital Health – Hope or Hype” from the esteemed Drs. Howard Wolpert and Joyce Lee, as well as from the inimitable Chris Bergstrom, now of BCG. We also include commentary from the DiabetesMine D-Data Exchange (FDA was a special guest!) as well as a slew of announcements from Medtronic (updates on the next-gen CareLink Pro and Glooko pump/CGM compatibility). For more on these and more (a total of ten highlights and three honorable mentions), please see below. For what the rest of the meeting has in store, don’t forget to check out our preview and ADA resource hub for everything you need for the next five days. ;>

Diabetes Technology Top Five Highlights

1. In “Digital Health – Hope or Hype?” the Joslin Clinic’s Dr. Howard Wolpert gave a masterful presentation on the state of digital health, and shared his view that technology should help shift the field away from traditional, prescriptive approaches to diabetes care and toward improving glucose control promoting patient behavior change though more interactive coaching that targets individual problem areas.

2. Dr. Joyce Lee (University of Michigan, Ann Arbor, MI) provided an overview of the data from her team's fascinating Nightscout user survey, highlighting the value of lead-user innovation for driving progress in patient-centered technology – “People in the community will not wait for healthcare providers to come up with technology. They won’t wait for regulators to regulate, or companies to innovate. They need solutions now.”

3. BCG’s Mr. Chris Bergstrom opened the “Digital Health – Hope or Hype?” session by discussing in a whirlwind tour de force the past, present, and future of digital health. He ultimately  concluded that there is no “silver bullet” for the field and that the solutions of the future will instead provide clinicians with a diverse toolbox from which to individualize therapy.

4. The “off-campus” standing-room-only DiabetesMine D-Data Exchange was headlined by: a vision for interoperable, component AP systems (FDA’s Dr. Courtney Lias); a standing ovation for OpenAPS developer Mark Wilson; a masterful overview of different closed-loop systems from Stanford’s Dr. Trang Ly; a strong desire for customizable closed loop algorithm glucose targets; and more need for industry to engage with and learn from the DIY community.

5. Medtronic had a big day of diabetes data announcements: (i) next-gen CareLink Pro reports will help optimize basal and bolus pump settings and launch this summer; (ii) Glooko pump/CGM compatibility is finally done and will be out in July; (iii) the name of the IBM Watson app is “SugarWise,” the first-gen will launch this summer, and it will only do retrospective pump/CGM data analysis at launch; and (iv) a new beta app with Nutrino has launched to incorporate food and CGM data via MiniMed Connect. There was also an announcement about a new partnership with Canary Health though details were scarce.

Diabetes Drug Top Five Highlights

1. A high-powered group of researchers and industry representatives gathered in a closed session this morning to hear presentations from the most recent recipients (six) of the ADA’s Pathway to Stop Diabetes grants.

2. Results from a phase 2 proof of concept study (n=50) of combination therapy with AZ’s Farxiga (dapagliflozin) and Bydureon (exenatide once weekly) demonstrated significant ~4 kg weight loss and glycemic improvements vs. placebo in patients with obesity but not diabetes.

3. Dr. John Blundell (University of Leeds, UK) presented positive results on reductions in energy intake and appetite with once-weekly GLP-1 agonist semaglutide in people with obesity.

4. Dr. Joachim Tillner (Sanofi, Paris, France) presented positive phase 1 data for Sanofi’s GLP-1/glucagon dual agonist SAR425899 demonstrating a reassuring safety/tolerability profile, a half-life consistent with once-daily dosing, and improvements in glycemia and body weight.

5. Dr. Rury Holman (University of Oxford, UK) shared that analysis for a ~250 patient feasibility study for the GLINT metformin cardiovascular outcomes trial is almost complete.

Honorable Mentions

• On an exciting note, the ADA announced its acquisition of Intelligent Medical Decisions (iMD) to expand the capabilities of the Diabetes INSIDE quality of care improvement initiative.
• Dr. Alan Cherrington provided new details on the six-month data for Fractyl’s Revita Duodenal Mucosal Resurfacing procedure for type 2 diabetes.
• During his state-of-the-art lecture on the future of technology in the management of inpatient diabetes, Dr. David Klonoff briefly referenced the Diabetes Technology Society’s (DTS) new BGM Surveillance Program and recently published DTS Cybersecurity Standard for Connected Diabetes Devices.

Diabetes Technology Top Five Highlights

1. Digital Health is About Interactive Coaching that Targets Individual Problem Areas – Dr. Howard Wolpert

Dr. Howard Wolpert’s (Joslin, Boston, MA) masterful presentation on the state of digital health shared his belief that technology is going to shift us away from traditional, prescriptive approaches to diabetes care and towards more interactive coaching that targets individual problem areas. The presentation revealed his great enthusiasm for digital health and neatly boiled down the key elements of clinical success in diabetes management into two factors: (i) improving the mechanics of glucose control [e.g., data analytics, insulin/medication optimization]; and (ii) promoting patient behavior change [e.g., identifying problem areas, triggering engagement in self-care]. We’re very excited by this sense and hope that HCPs will be able to get enough funding to make this worthwhile. Digital health solutions are particularly promising in Dr. Wolpert’s view because they target both these niches, whereas the majority of clinical contact focuses on the former (e.g., prescribing an insulin dose, telling patients what to do). Dr. Wolpert acknowledged that he himself only began to appreciate the promise of digital health when he came to terms with the value of enhancing self-management – “What I began to appreciate is that the biggest change in glucose control in my patients came not when I adjusted their insulin dose but when THEY began identifying their own glycemic trouble spots … yet we rarely assess this.” He suggested that technology creates uniquely teachable moments and allows patients to engage in their own care, thereby creating tighter feedback loops between real-world choices and outcomes (or as Dr. Bill Polonsky likes to say, “Makes something click”). Ultimately, Dr. Wolpert asserted that current therapeutic approaches rely far too heavily on providing data to patients without telling them what it means and teaching them to use it effectively – and what good is that, he asked? Dr. Wolpert’s concluding remarks stressed that connecting the dots is where digital health solutions can turn the tide in diabetes care, making patients the ultimate managers of their day-to-day care.

2. UMich’s Dr. Joyce Lee on Nightscout – People with diabetes simply will not wait

Dr. Joyce Lee (University of Michigan, Ann Arbor, MI) provided an overview of her team's fascinating Nightscout user survey, highlighting the value of lead-user innovation for driving progress in patient-centered technology – “People in the community will not wait for healthcare providers to come up with technology. They won’t wait for regulators to regulate, or companies to innovate. They need solutions now.” She referenced the strong traction the Nightscout movement has gained over the past few years, noting that since launch in 2013, over 25,000 patients from around the world have reported using the system. According to Dr. Lee, the private Facebook group for CGM in the Cloud now has 18,000 members, making it one of the largest groups representing diabetes on Facebook. Dr. Lee summarized findings from a University of Michigan-led survey of a subset of the Facebook group (n=1,276) – we first saw these results at the 2015 DiabetesMine Innovation Summit and D-Date Exchange, where we were impressed by Nightscout's positive impact on CGM adoption, improved quality of life, and reduction in self-reported A1c. Notably, a striking ~20% of CGM in the Cloud members started CGM as a result of Nightscout and ~9% restarted CGM as a result of Nightscout. Survey respondents reported a significant improvement in quality of life metrics, and a majority stated that they found the technology "extremely empowering" and "not at all prying.” Self-reported A1c also indicated that glycemic control improved meaningfully (0.7%-1.2%) pre- vs. post-Nightscout. In addition, survey results suggested that users largely replaced their BGMs with CGM data for insulin dosing; respondents reported taking fewer blood sugar checks per day and giving a greater number of insulin boluses without a meter blood sugar on Nightscout. This reinforces our impression that many patients use CGM for insulin dosing regularly, a fact that has become increasingly pertinent given the upcoming FDA Advisory Committee meeting to vote on a replacement label claim for Dexcom’s G5 CGM.

• Dr. Lee also discussed the “maker movement” mentality, stressing its role in unleashing a cascade of creativity and innovation. For Nightscout, this has resulted in a plethora of devices, codes, and functionality, providing opportunities for customizing the glucose monitoring experience. [The same is true of the DIY OpenAPS community, which has a lot of overlap with the Nightscout developers.] Dr. Lee noted that patients are also “tinkering” with the system’s hardware, creating solutions such as xDrip, a tiny alternate CGM receiver that can be used to receive data from the Dexcom G4 transmitter and send it to other devices.
• According to Dr. Lee, the current issue is whether or not Nightscout will disappear now that the FDA has approved commercial solutions that display CGM data on personal devices (Dexcom G4/G5, MiniMed Connect). She believes that Nightscout’s popularity will persist, given the high rate of new members entering the community. We believe the influx speaks to the community that Nightscout has created; the wider device compatibility and more “glanceable” and customizable displays on smartwatches; and to the overall message that Nightscout brings to the diabetes community: an empowering solution to help patients and caregivers monitor glucose with increased safety and more peace of mind.
• Dr. Lee’s presentation echoed a valuable JAMA viewpoint she recently coauthored, which details Nightscout’s patient-driven founding, the system’s rapid growth, and its impact on changing the current definitions of health production and patient engagement.

3. Chris Bergstrom on Digital Health: No Silver Bullet, But a Bigger Toolbox To Individualize Therapy

BCG’s Mr. Chris Bergstrom discussed the past, present, and future of digital health, and concluded that there is no “silver bullet” for the field and that the solutions of the future will instead provide clinicians a diverse toolbox from which to individualize therapy. His commentary described how the field is poised to make a very real impact on healthcare in the near future, with examples ranging from Uber to Airbnb showing that “digital disruption has proven powerful already!” We loved his views about Uber and Airbnb and how the administrative burdens have been removed in those areas – it would be tremendous if there were such a tool to reduce administrative burden for HCPs! He characterized the previous half-decade as a time of successful idea generation in diabetes that has resulted in dramatic technological progress, suggesting that such progress has and continues to build an infrastructure that will be critical to the success of digital healthcare solutions. He drew an analogy to how the proliferation of computers and reliability of the postal service served as lynchpins for the growth of home delivery services (e.g., Amazon, eBay), noting that digital health is at the cusp of having the infrastructure in place to grow exponentially. He further stressed the way that various stakeholders in medicine (FDA, entrepreneurs, providers, patients) have become increasingly comfortable with digital health as a concept, citing a number of factors – (i) President Obama recognizing Tidepool’s Mr. Howard Look as a Champion for Change; (ii) five-fold growth in EMR adoption between 2009 and 2015; (iii) forward-looking FDA mobile app guidance documents; (iv) Abbott launching FreeStyle Libre (“an exciting new technology”); and much more  – as evidence that the foundation for digital health in diabetes is actively being built. In closing, Mr. Bergstrom reminded us of the potential of digital health solutions to “offload administrative burden,” and in his ideal future, suggested that technology would allow clinicians to practice at the pinnacle of their abilities rather than getting “bogged down in things they are overqualified to be doing [e.g., paperwork, etc.].” Yessir – this is the dream! For more details from Mr. Bergstrom’s whirlwind tour of digital health, please see our full write-up below.

4. DiabetesMine D-Data Wows on Automated Insulin Delivery Regulation, DIY Community, Needs, Strengths + Weaknesses

The standing-room-only DiabetesMine D-Data Exchange gathered some of the best minds in diabetes technology, headlined by: a vision for interoperable, component AP systems (FDA’s Dr. Courtney Lias); a standing ovation for OpenAPS developer Mark Wilson; a masterful overview of different closed-loop systems from Stanford’s Dr. Trang Ly; a strong desire for customizable closed loop algorithm glucose targets; and more need for industry to engage with and learn from the DIY community. This six-hour day was jam packed with learning and we’ll be back in our full report with even more learning from the industry panel discussion (Animas, Beta Bionics, Bigfoot, Dexcom, Insulet, Medtronic, moderated by Howard Look).

• FDA’s Dr. Courtney Lias shared a strikingly optimistic goal to build an infrastructure for interoperable, modular, component artificial pancreas systems. “We don’t see a way artificial pancreas can be what it needs to be without this. I’m sharing our intention of solving this problem.” As she noted at last week’s AP Webinar, the current regulatory paradigms are easier for single companies submitting a combined pump/CGM/algorithm system (e.g., Medtronic’s MiniMed 670G). Showing a “FACE PALM” slide, she noted that this “system” framework could hamper innovation and product iteration. Dr. Lias highlighted Dexcom’s pump partnerships with Animas and Tandem as two examples, which were slowed by months of legal contracts and ironing the nuances of responsibility and regulation – a very inefficient process. Dr. Lias envisioned a day with standardized, interoperable devices, allowing patients to swap in different system components (pumps, CGMs, and algorithms; see picture below). She outlined a list of current challenges that FDA and the scientific community/industry must address (see table below), noting this might take ~10-15 years to totally solve. [Many in the audience thought it could be faster.] More details below, including a picture of her vision.
• Mark Wilson received a standing ovation after his talk on the do-it-yourself (DIY) OpenAPS, noting that open, interoperable diabetes devices will facilitate an ecosystem of diabetes innovation that manufacturers could never have imagined – and that will help drive adoption and dramatically improve products. Mr. Wilson predicted that the first pump to securely enable patients to access it (e.g., from a phone app) will see tremendous success. As an example of what devices with open APIs can offer, Mr. Wilson cited Fitbit’s wireless scale, Aria – the scale connects to Wi-Fi and sends the data to the cloud, allowing developers to connect to it and build novel apps that use the data. BeeMinder allows a user to connect their credit card and Fitbit scale seamlessly: “If I don’t weigh 160 lbs in three months, charge me $150. Fitbit won’t think of that, but it adds value to Fitbit. This is what we need from diabetes devices.” See a picture below of what Mr. Wilson hopes to see, along with a few more thoughts from his talk, including the $13,000 reward being offered to crack the OmniPod’s communication protocol!
• There was consensus that closed-loop devices should: (i) include algorithms with customizable glucose targets; (ii) insulin-on board on the home screen; and (iii) have highly adjustable alarm settings. The patient panel was clear that customizing an algorithm’s aggressiveness is very key – some patients want more control, particularly because early-generation systems are more conservative. Indeed, Dr. Trang Ly pointed to this as an area for improvement in the Medtronic MiniMed 670G, which targets 120 mg/dl and does not allow the user to lower the target. Of course, there is a tough balance between customizability and simplicity – tweaking every parameter might be ideal for early adopters, but will add too much complexity that could hinder adoption. Dr. Ly felt strongly that systems should include insulin-on-board, a sentiment we agree with.
• Stanford’s Dr. Trang Ly provided an outstanding overview of artificial pancreas systems, calling the technology “transformative,” characterizing first-gen product algorithms as “conservative,” and summarizing systems’ strengths and areas for improvement. Dr. Ly argued that the biggest challenge Medtronic’s MiniMed 670G faces is managing expectations (“This is not going to cure you. That will be their biggest problem”). She also noted that MiniMed Connect doesn’t work with this device right now, and the lack of an adjustable glucose target needs to improve. On the bright side, she noted that the 670G is a very nicely integrated system and the pivotal trial is complete, putting it first in line to market. We’ll see the data tomorrow!

• The DIY community is dying to interact with industry, though companies are still resistant. OpenAPS co-creator Dana Lewis indicated that industry’s regulatory concerns are a “phantom worry.” Dr. Courtney Lias urged the DIY community to talk to the FDA. Mr. Lewis argued that companies can still talk to and learn from the OpenAPS community, even if it is not an “approved” product – engaging does not imply support or anything illegal. Dr. Lias said the FDA “comes from a place of understanding,” but OpenAPS technically falls under FDA jurisdiction. The agency has enforcement discretion and will regulate based on risk – FDA may not choose to spend resources on someone building a system for their own personal use. However, the Agency does want a level playing field: “There is no difference between a movement developing a platform, and a small company developing a platform. We are definitely open to talking about the community, and how we cover the responsibility piece and make sure adverse events are reported...I would push the patient community to start solving the responsibility piece, even if it’s not the current FDA path, we are open to talking about that. There are lots of ways to meet the FDA requirements...Vendors are skittish because of the area of responsibility....We can solve problems by talking together, assuming FDA will or won’t do this. I would invite people to talk with me about it, and encourage bigger discussion between this community and FDA – how do we get you what you want, and how do we get what we need?”

5. Medtronic Announces Next-Gen CareLink Reports to Optimize Pump Settings, Glooko Compatibility, IBM Watson App Named SugarWise, Food App Partner: Nutrino

Medtronic had a big day of diabetes data announcements: (i) next-gen CareLink Pro reports will help optimize basal and bolus pump settings and launch this summer; (ii) Glooko pump/CGM compatibility is finally done and will be out in July; (iii) the name of the IBM Watson app is “SugarWise,” the first-gen will launch this summer, and it will only do retrospective pump/CGM data analysis at launch; (iii); and (iv) a new beta app with Nutrino has launched to incorporate food and CGM data via MiniMed Connect.

• Next-gen CareLink Pro reports to optimize basal and bolus settings: These will launch this summer and will be on display in the Medtronic exhibit booth tomorrow. The software will identify optimal insulin:carb ratio, insulin sensitivity factor, and necessary basal rate changes (isolating times of fasting/steady-state) – basically the dream of all patients on pumps and their care providers. Providers will get suggestions on time and direction of change. These reports sound similar to what DreaMed is doing with Glooko and could really improve pump settings, which remain sub-optimal for many (if not most) patients. We’ll dig into them tomorrow in the Exhibit Hall.  
• Glooko compatibility: See screenshots in the detailed discussion below, which will officially launch in July. The user interface looks great and adds Glooko’s new “Personal Advisor,” bringing new pattern recognition features in the patient-facing app (high and low trends by time of day, best day, fun emoji faces, etc.). This integration has been more than a year in the making (Medtronic invested in Glooko last March) and we give HUGE kudos to Glooko (and particularly Holly McGarraugh) for break open the Medtronic CareLink data silo. A huge win for diabetes data! Glooko is riding impressive momentum after its partnership with Insulet, and management told us it is in more than 1,000 US clinics now. We’ll have a closer look in the exhibit hall tomorrow.
• Medtronic/IBM Watson Health app, SugarWise: The app is officially named “SugarWise (bringing insight to blood sugars) and is still expected to launch this summer. The first generation app will analyze retrospective data and provide insights based on past CGM, insulin, and nutrition data: “William, the last few times you did this, then this happened.” The example from last week’s Analyst Meeting said, “In the last 30 days, high glucose pattern found usually after glazed donut for breakfast.” A future-generation version will add the hypoglycemia prediction feature that Medtronic we first saw at CES in January (“In the next two hours, there is a high likelihood that you will go low”). It’s a shame the latter isn’t included in this first-gen version, as it seems fairly low risk. On the other hand, getting the accuracy of future hypoglycemia prediction is only one piece of the puzzle – alarm fatigue and data entry burden are both important questions with this feature. Medtronic and IBM have now worked on the hypoglycemia prediction feature with a dataset of 10,000 anonymous patients, showing preliminary prediction accuracy of 75%-86% within a two-to-four hour window.
• Nutrino food app partnership: Medtronic and Nutrino launched a beta food app today for customers who use MiniMed Connect, providing an individualized picture of how daily food intake and other measures impact glucose levels – see the screenshot below, the compelling video here, and download the app here. Nutrino imports the CGM and insulin data seamlessly from MiniMed Connect (from a Medtronic pump) and identifies how different foods affect blood glucose levels, allows patients to take meal pictures, scan bar codes, carb count, and more. Nutrino also gives a FoodPrint that shows how daily food intake, activity, sleep and other parameters affect glucose levels – whoa! From what we can tell, it’s a more built out version of Meal Memory, and it can read data from Apple’s HealthKit (though it doesn’t read data from Dexcom CGM from what we can tell). This app sounds impressive and we’ll be back with more details after we’ve had more time to play with it.

Diabetes Drug Top Five Highlights

1. ADA Pathway to Stop Diabetes Grant Recipients

A high-powered group of researchers and industry representatives gathered in a closed session this morning to hear presentations from the most recent recipients of the ADA’s Pathway to Stop Diabetes grants. Introductory remarks by ADA President Dr. Des Schatz and Dr. C. Ronald Kahn (Joslin Diabetes Center, Boston, MA) emphasized the program’s goals of promoting long-term, transformational change in diabetes care and encouraging collaboration. They also highlighted the selectiveness of the program: the 17 grant recipients selected thus far were chosen from a pool of 330 applicants, and as Dr. Kahn put it, “those 330 people were all pretty damn good.” The introductory speakers also noted that there was a concerted effort to focus attention on this program at this year’s ADA, with a dedicated poster session on Sunday and an oral presentation session on Monday in addition to this symposium. We remain very impressed with the Pathway initiative, which awards grants of up to $1.6 million over five to seven years to young diabetes researchers working on innovative projects focused on everything from neuronal regulation of feeding behavior to impaired wound healing. The program is supported by several heavy hitters in the diabetes industry, including Sanofi, Novo Nordisk, AstraZeneca, and Lilly, and we imagine this could make it easier for the researchers to eventually translate their findings into novel therapies. We think this program can play a major role in shaping the next generation of KOLs in diabetes. We also hope it can promote a more diverse group of leaders compared to the current crop (in a sign of some progress, 35% of the Pathway grant recipients are women compared to 26% of the mentors). See below for a list of the 2016 grant recipients, and see the detailed discussion section for a more detailed overview of their work, though we unfortunately cannot provide specifics on the data presented this morning due to the closed nature of the session.

• Initiator Awards (intended for postdoctoral scientists establishing independent careers)
  
  • Sui Wang, PhD (Harvard Medical School, Boston, MA)
  • Phillip James White, PhD (Duke University, Durham, NC)
• Accelerator Awards (intended for early-career investigators pursuing high-risk but promising projects)
  
  • Daniel Ceradini, MD (New York University, New York, NY)
  • Zachary Knight, PhD (UCSF, San Francisco, CA)
  • Praveen Sethupathy, PhD (UNC, Chapel Hill, NC)
• Visionary Awards (intended for established investigators in other research areas)
  
  • Andrew Scharenberg, MD (Seattle Children’s Hospital, Seattle, WA)

2. Weight Loss and Glycemic Improvements with Dapagliflozin/exenatide Combination Therapy in Patients with Obesity

Results from a phase 2 proof of concept study (n=50) of combination therapy with AZ’s Farxiga (dapagliflozin) and Bydureon (exenatide once weekly) demonstrated significant ~4 kg weight loss and glycemic improvements vs. placebo in patients with obesity but not diabetes. Participants in the double-blind, single-center study were randomized to receive either active treatment or double placebo for 24 weeks, followed by a 28-week open-label extension study; data from the extension study will be presented at EASD in September. After 24 weeks, the combination led to significant placebo-adjusted weight loss of 4.1 kg (baseline weight = 103-106 kg [227-234 lbs]; baseline BMI = 35-36; p=0.0007) or 4.2% (p=0.0005). As in most obesity drug trials, there was a wide range of responses, but far more patients achieved ≥5% weight loss with the active treatment than with placebo (36% vs. 4%). MRI analysis of body composition showed that almost all of the weight loss was due to loss of adipose tissue, with no significant change in lean tissue. The combination also produced a modest but significant 0.2% placebo-adjusted A1c reduction (baseline = 5.6%, p=0.0004), a significant drop in the proportion of patients with impaired fasting glucose and impaired glucose tolerance, and a significant placebo-adjusted blood pressure reduction of 6.4 mm Hg (p=0.026). Adverse events were fairly balanced, with slightly more GI side effects in the active treatment group.

• These results are encouraging, though as noted during Q&A, the real test will be how the combination stacks up against each of its components alone. AZ is currently conducting a phase 3 study (n=660) of that comparison in patients with type 2 diabetes that is expected to complete in December 2017 (primary completion May 2016). As presenter Dr. Jan Eriksson (Uppsala University, Sweden) noted, GLP-1 agonist/SGLT-2 inhibitor combinations are very appealing for obesity due to their complementary mechanisms of weight loss (calorie loss with the SGLT-2 inhibitor and reduced appetite/caloric intake with the GLP-1 agonist). The same could also be said for glycemic control, as the reduction in glucagon production with GLP-1 agonists could help mitigate the increased glucagon production that blunts some of the efficacy of SGLT-2 inhibitors. We expect AZ to focus primarily on type 2 diabetes with this combination but find the potential in obesity very interesting as well, particularly for a GLP-1 agonist with more potent weight effects like Novo Nordisk’s Saxenda (liraglutide 3.0 mg) or semaglutide.

3. Positive Results for Semaglutide in Obesity

Dr. John Blundell (University of Leeds, UK) presented positive results on reductions in energy intake and appetite with once-weekly GLP-1 agonist semaglutide in people with obesity. This double-blind, crossover study examined the mechanisms of weight loss of semaglutide (dose-escalated to 1.0 mg) vs. placebo in 30 participants with obesity and without type 2 diabetes (baseline BMI of 34 kg/m²). At 12 weeks, the results found a reduction in body weight, with decreases in energy intake, appetite, and food intake along with overall improved control of eating. Specifically, findings demonstrated that ad libitum energy intake was lower with semaglutide vs. placebo at lunch (5 hours after standardized breakfast), evening meal, and snacks with relative reductions of 35%, 18%, and 22%, respectively. In addition, the semaglutide group achieved weight loss of 5 kg (with greater loss of fat mass compared to lean mass) vs. a small increase of 0.97 kg with placebo. Fasting overall appetite scores also indicated reduced appetite with semaglutide vs. placebo (p=0.0023), while nausea ratings were similar – suggesting that this effect was independent of side effects. Additionally, results from the overall appetite-suppression score and control of eating questionnaire indicated less cravings and greater control of eating. Notably, participants had greater reductions in energy intake of food groups of high fat and traditionally more “appealing” foods, which reflected the results from the Leeds food preference task. Dr. Blundell noted that the semaglutide group experienced a reduction in resting metabolic rate, but the difference was not statistically significant. These findings further confirm to us the impressive versatility of semaglutide, as the product has been suggested to be studied in several indications beyond type 2 diabetes, including NASH, obesity, and a range of macrovascular and microvascular complications – see more on this from our Novo Nordisk 1Q16 report. We have certainly seen significant enthusiasm for the GLP-1 agonist class within obesity – as already pioneered by Novo Nordisk’s Saxenda (liraglutide 3.0 mg) – and the eating behavior-specific findings from this study direct us back to potential mechanisms within the brain and its reward circuitry, which is marking itself as a fast growing area of research for obesity.

4. Full Phase 1 Data for Sanofi’s GLP-1/glucagon dual agonist SAR425899

Dr. Joachim Tillner (Sanofi, Paris, France) presented positive phase 1 data for Sanofi’s GLP-1/glucagon dual agonist SAR425899 demonstrating a reassuring safety/tolerability profile, a half-life consistent with once-daily dosing, and improvements in glycemia and body weight. We saw some of this data at the Keystone Symposia on Molecular and Cellular Biology meeting in April demonstrating significant reductions in weight (-5.5 kg [~12 lbs] vs. -2.4 kg [~5.2 lbs]; p<0.001) and “clear” (p-value not specified) reductions in A1c (-0.59% vs. +0.06%) and fasting plasma glucose (-55 mg/dl vs. -22 mg/dl) with SAR425899 vs. placebo after four weeks in 36 patients with type 2 diabetes. In this presentation, Dr. Tillner also shared data from the other two parts of Sanofi’s phase 1 program for the candidate: a single ascending dose study in 32 healthy males and a three-week multiple ascending dose study in 40 healthy males. The three studies together demonstrated a safety/tolerability profile for SAR425899 that was comparable to GLP-1 single agonists. GI side effects were the most prominent adverse events (nausea was the limiting factor for dose escalation in the single ascending dose study) and the drug produced an increase in heart rate in the same range as previously studied GLP-1 agonists. Based on these results, Dr. Tillner expressed confidence that GLP-1/glucagon dual agonism works, despite his initial incredulity at the idea of a diabetes treatment that stimulates glucagon production. He stated that Sanofi’s goal for SAR425899 is to equal GLP-1 agonists in terms of glycemic control and surpass them in terms of weight reduction. We assume the company is planning to pursue a type 2 diabetes indication for the candidate, but we wonder whether there could be any potential in obesity or prediabetes as well. GLP-1/glucagon dual agonists have attracted a significant amount of industry interest and we will be curious to see how the various candidates can differentiate themselves – see our competitive landscape page for an overview of the current field.

5. Feasibility Study Analysis for GLINT Metformin Cardiovascular Outcomes Trial Nearly Complete

Dr. Rury Holman (University of Oxford, UK) shared that analysis for a ~250 patient feasibility study for the GLINT metformin cardiovascular outcomes trial is almost complete. This is smaller than the ~500 patient feasibility trial Dr. Holman previously discussed when he introduced the GLINT study (which he is Chief Advisor and previously a co-chair for) at Diabetes UK 2013 and EASD 2014. The GLINT trial hopes to enroll ~12,000 patients with prediabetes and high cardiovascular risk and assess primary prevention of a 3-point MACE primary endpoint (cardiovascular death, non-fatal MI, non-fatal stroke). Secondary endpoints include incident cancer and new-onset diabetes (inspired by some less-rigorous evidence that metformin can reduce incidence of both). Dr. Holman shared that the larger trial is currently seeking funding, noting that industry has little incentive to fund such a large trial for an old medication. Dr. Holman suggested that the impetus for the trial comes from the lack of clear understanding of the true benefits and risks of metformin, despite its long history of clinical use. He reviewed UKPDS data that showed a potential potent cardiovascular benefit for metformin, though he emphasized that the study was underpowered and “some think the data is magic, a fluke that can never be replicated – because nobody has tried to replicate it.” On the flip side, he also reviewed UKPDS data that showed an increased cardiovascular risk with metformin and sulfonylurea combination therapy compared to sulfonylureas alone, though he emphasized that the event rate was low in the trial itself and that the risk was attenuated in longer-term follow-ups as the event rate rose. Overall, Dr. Holman supported the use of metformin as a first-line therapy and noted that many smaller studies and decades of clinical experience seem to suggest that the drug is safe, but he believes there is a need for a long-term study such as GLINT to more definitively understand the relationship between metformin and cardiovascular disease, cancer, and new-onset diabetes.

• We see the GLINT trial as a potential very ambitious parallel to the recent IRIS trial, which demonstrated a cardiovascular benefit for generic TZD pioglitazone in patients with prediabetes and a history of stroke or transient ischemic attack (TIA). The IRIS trial was similarly driven by a group of academic researchers, though it was a much smaller trial (n=3,876) in a higher risk participant population. That trial demonstrated significant risk reduction for the primary endpoint of fatal and non-fatal stroke and MI, but it did not meet its secondary endpoint of 3-point MACE reduction. As a much larger trial with ambitions to demonstrate a more difficult primary prevention benefit, the GLINT trial will likely take many more years and be much more expensive. At the time of the trial announcement, Dr. Holman estimated that data would be available in 2022. We see IRIS and GLINT as an encouraging indication of interest in revisiting the cardiovascular risk reduction potential of older glucose-lowering medications and we hope that GLINT is successful in winning the funding to establish the long-term outcomes associated with metformin. We’re also intrigued by the possibility that long-term clinical trial evidence establishing a diabetes preventive effect for metformin or pioglitazone could pave the way for approval of therapies for people with high-risk prediabetes. Dr. Silvio Inzucchi will present more in-depth data on the 52% relative risk reduction in new diabetes diagnosis (p<0.001) seen in the IRIS trial at an oral presentation on Tuesday (380-OR).

Honorable Mentions

Honorable Mention: Dr. David Klonoff’s Update on DTS’s BGM Surveillance Program and Cybersecurity Standard

During his state-of-the-art lecture on the future of technology in the management of inpatient diabetes, Dr. David Klonoff briefly referenced the Diabetes Technology Society’s (DTS) new BGM Surveillance Program and recently published DTS Cybersecurity Standard for Connected Diabetes Devices. He shared that the DTS has started testing its BGM Surveillance Program to assess the accuracy of off-the-shelf, FDA-cleared BGMs – we first reported on this yesterday – though he added a new detail that a total of 18 BGMs will be tested whose sales make up 90% of all meter sales in the US. (We still do not know which meters these are, but assume its Abbott, Ascensia, LifeScan, Roche, and popular store brand meters.) Dr. Klonoff also stated that popular hospital BGMs will be tested with the new DTS Surveillance Program to improve the quality of point of care capillary blood glucose testing. We wonder if there is enough overlap between popular point-of-care and hospital meters that this will not require too significant an additional investment – especially considering how long it took the organization to amass the requisite funding for the point-of-care program. In addition, Dr. Klonoff shared that the DTS’s Cybersecurity Standard for Connected Diabetes Devices was published last month, consistent with timing first shared at DTM 2015. As expected, the document contains a set of performance requirements to improve cybersecurity by describing the scope of the cybersecurity challenge, providing a generic framework for how devices need to be protected, and creating an assurance plan for how to get there (e.g., accrediting labs to test devices). He stated his belief that manufacturers who voluntarily test with DTSec will be able to increase their sales and profits, though we’re not entirely positive how results are going to be interpreted, whether industry will buy in to the process, and if government agencies will pay attention. We agree that cybersecurity is an important component of device design, but we’re not sure if DTS is uniquely qualified to perform such testing, or whether extra security standards will negatively impact device design (e.g., passwords, two-actor authentication, etc.). How much will it cost manufacturers to test their devices? Will standards constantly need to be updated to reflect technological progress? If results expose devices with poor security, will FDA take action, or will payers eliminate coverage of those products? For more coverage of the DTS cybersecurity standard, please see our coverage from DTM 2015.

Honorable Mention: ADA Acquires Intelligent Medical Decisions

The ADA announced its acquisition of Intelligent Medical Decisions (iMD) to expand the capabilities of the Diabetes INSIDE quality of care improvement initiative. Diabetes INSIDE harnesses population health analytics, data-driven education, and quality improvement science, tools, and techniques to promote high-quality diabetes care in large health systems across the nation. The interventions used in the program are based on the ADA’s Standards of Medical Care in Diabetes (last updated in March), which includes an evidence grade of A-E for every one of its recommendations. In terms of outcomes, the ADA’s announcement shared that the Diabetes INSIDE program has been able to demonstrably improve patient engagement, reduce A1c, and improve overall blood sugar control at the population level. We expect that more details on the outcomes data will be available in Monday’s poster “Diabetes INSIDE: A National Quality Improvement (QI) Initiative Guiding Large Health Systems to Improve Diabetes Care (671-P).” The ADA and iMD have been partnered to deliver Diabetes INSIDE for the last five years and this acquisition solidifies the relationship, suggesting that these programs are here to stay. Under the terms of the acquisition, the ADA will hire all current iMD employees and acquire all its assets. Of late, the use of big data to better understand and improve diabetes care and outcomes has attracted significant attention and investment from diverse parties. For example, Sanofi entered into a high-profile partnership with Google to harness population-level insights to improve its therapies.

Honorable Mention: More Details on Six-Month Data for Fractyl - Can Efficacy be Sustained?

Dr. Alan Cherrington (Vanderbilt University, Nashville, TN) provided new details on the six-month data for Fractyl’s Revita Duodenal Mucosal Resurfacing procedure for type 2 diabetes. The procedure, which recently received CE Mark approval, involves ablation of a portion of the duodenum via a technique that the company has characterized as similar to an upper endoscopy. Dr. Cherrington shared that significant A1c reductions occurred in both patients with a baseline A1c >10% (mean baseline A1c=~11%) and those with a baseline A1c of 7.5%-10% (mean baseline A1c=~9%) who had a “long” segment of more than 9 cm ablated (mean= ~9.3 cm). The procedure demonstrated peak efficacy at three months, with A1c reductions of ~3.5% in the higher baseline A1c cohort and ~2% in the lower baseline A1c cohort. However, the effect was substantially attenuated at six months, resulting in a final six-month A1c reduction of 2.1% in the higher baseline A1c group and 1.0% in the lower baseline A1c group. These A1c reductions are not as strong as we might have hoped, given the high starting A1c and the relatively invasive procedure (as compared to a more traditional oral or injectable medication). We imagine that Fractyl will need to demonstrate sustained efficacy in order for the procedure to appeal to a large number of patients, and we hope future trials can provide more clarity on this point. Dr. Cherrington also shared that the Revita DMR procedure improved insulin sensitivity (as measure by HOMA-IR) and metabolomic analysis indicated improved insulin sensitivity, reduced oxidative stress, and improved mitochondrial function following the procedure.

• We previously saw six-month data demonstrating a mean A1c reduction of 1.2% (p<0.001) at six months, as well as improvements in fasting glucose (non-significant, p=0.09), postprandial glucose (p<0.05), and weight loss (-1.8 kg, p<0.05) in the cohort of patients who had a “long” segment ablated. Fractyl also recently presented data at the EASL International Liver Conference demonstrating improvements in hepatic transaminase levels (AST and ALT specifically, p<0.01) with the procedure.

Detailed Discussion and Commentary

DiabetesMine D-Data Exchange

FDA on Interoperability & artificial pancreas Progress: Where GUidance Can Take US

Courtney Lias, PhD (FDA, Silver Spring, MD)

FDA’s Dr. Courtney Lias shared a strikingly optimistic goal to build an infrastructure for interoperable, modular, component artificial pancreas systems. “We don’t see a way artificial pancreas can be what it needs to be without this. I’m sharing our intention of solving this problem.” As she noted at last week’s AP Webinar, the current regulatory paradigms are easier for single companies submitting a combined pump/CGM/algorithm system (e.g., Medtronic’s MiniMed 670G). Showing a “FACE PALM” slide, she noted that this “system” framework could hamper innovation and product iteration. Dr. Lias highlighted Dexcom’s pump partnerships with Animas and Tandem as two examples, which were hampered by months of legal contracts and ironing who is responsible when things go wrong – a very inefficient process. Dr. Lias envisioned a day with standardized, interoperable devices, allowing patients to swap in different system components (pumps, CGMs, and algorithms; see picture below). She outlined a list of current challenges that FDA and the scientific community/industry must address (see table below), noting this might take ~10-15 years to totally solve. [Many in the audience thought it could be faster.] It was clear that device communication standards are mission critical in all of this, leading us to wonder how Dr. Joe Cafazzo’s and Melanie Yeung’s work in Toronto on diabetes device standards could be integrated into commercial products. Dr. Lias concluded that FDA wants to be the “lead penguin” on artificial pancreas component interoperability, which might even include forward-looking guidance to pave an easier path for interoperable products. Nice! We were highly impressed with her open and forward-looking perspective, and wonder if industry will consider more modular approaches to AP system design. Plug and play component AP systems could significantly enhance patient choice, spur innovation, and improve automated insulin delivery far more quickly than the current paradigm. This will be a further topic of discussion at the FDA/NIH Artificial Pancreas workshop in Washington, DC on July 6-7.

• “Mobile phones are a must. We’re very pro putting artificial pancreas systems on mobile phones.” The strikingly positive commentary was great to hear, since this has been an open question mark – what are the risks of patients dosing insulin from a phone? The devil is of course in the details here: will the algorithm sit on the phone and communicate to the pump and CGM separately, or will the phone simply act as a window to what’s happening in the fully integrated pump? We were definitely encouraged to hear optimism on this front, since it opens up so many advantages to developers: faster iteration (software updates), remote monitoring, better user experience, etc.

• Dr. Lias succinctly summarized the challenges around modular, component artificial pancreas systems, with a clear emphasis on the lack of device communication standards.  

#OpenAPS and the DRIVE to DIY Diabetes Technology

Mark Wilson (OpenAPS; Freelance Software Developer, San Francisco, CA)

Mark Wilson received a standing ovation after his talk on the do-it-yourself OpenAPS, noting that open, interoperable diabetes devices will facilitate an ecosystem of diabetes innovation that manufacturers could never have imagined – and that will help drive adoption and dramatically improve products. Mr. Wilson predicted that the first pump to securely enable patients to access it (e.g., from a phone app) will see tremendous success. As an example of what devices with open APIs can offer, Mr. Wilson cited Fitbit’s wireless scale, Aria – the scale connects to Wi-Fi and sends the data to the cloud, allowing developers to connect to it and build novel apps that use the data. BeeMinder allows a user to connect their credit card and Fitbit scale seamlessly: “If I don’t weigh 160 lbs in three months, charge me $150. Fitbit won’t think of that, but it adds value to Fitbit. This is what we need from diabetes devices.” He characterized OpenAPS as a “platform” that enables different devices, closed-loop algorithms, and data displays to be tailored to each patient’s preferences. Indeed, he boluses from his Apple Watch, and in addition to selecting quantity of carbs, he denotes whether it is a lollipop, taco, or pizza bolus. Mr. Wilson lamented the difficulty of accessing current devices, citing Ben West’s ultimately successful six-year quest (!) to hack into the Medtronic pump. There is even a $13,000 reward being offered to crack the OmniPod’s communication protocol! Mr. Wilson characterized this as a waste of time, subtracting valuable resources from building compelling user interfaces and new ways of managing diabetes. His diabetes device-as-car analogy beautifully explained the rationale for OpenAPS: “Diabetes is not about the car; it’s about the drive. There is a perception that DIY people are car fanatics, and we just have to tinker with our devices – we want the fancy rims. The reality is we were sentenced to drive, and we were given a car – clearly by someone who has never been behind the wheel. We [OpenAPS] happen to open up the car and hotwire it, and it makes our drive so much better.” We fervently hope some of the learning from OpenAPS will make it into the hands of industry. There are now 81 people on the system globally, collecting over a thousands hours of closed-loop data every day.

Glooko Screenshots

Medtronic/Nutrino Screenshot

Digital Health in Diabetes: Hope or Hype?

Digital Health and Diabetes

Chris Bergstrom (Associate Director, Digital Health, Boston Consulting Group)

Mr. Chris Bergstrom’s discussion of the past, present, and future of digital health described how the field is poised to make a very real impact on healthcare in the near future. He opened by impressing upon the audience the potential of digital health solutions, noting with examples from Uber to Airbnb how “digital disruption has proven powerful … the potential is HUGE!” He characterized the previous half-decade as a time of successful idea generation in diabetes that has resulted in dramatic technological progress, suggesting that such progress has and continues to build an infrastructure that will be critical to the success of the field. He drew an analogy to how the proliferation of computers and reliability of the postal service served as lynchpins of the growth of home delivery services (e.g., Amazon, eBay), noting that digital health is similarly at the cusp of having the infrastructure in place to grow exponentially. He stressed, too, the way that various stakeholders in medicine (FDA, entrepreneurs, providers, patients) have become increasingly comfortable with digital health in recent years, citing a number of factors – (i) President Obama recognizing Tidepool’s Mr. Howard Look as a Champion for Change; (ii) five-fold growth in EMR adoption between 2009 and 2015; (iii) FDA mobile app guidance documents; (iv) Abbott launching FreeStyle Libre (“an exciting new technology”); and much more  – as evidence that the foundation for digital health success is actively being built. He also predicted that digital health solutions are going to be particularly instrumental to clinical trials, helping the community recruit more efficiently and amass expanded, continuous data sets. Ultimately, he concluded that there is no “silver bullet” for the field and that digital health solutions of the future will instead provide clinicians a diverse toolbox from which to individualize therapy.

• Among many emerging technology he identified, Mr. Bergstorm shared great praise for Emminens’ chronic disease data management platform. We had never previously heard of this company, who has apparently partnered with Roche to bring a diabetes downloading/analysis software to Spain. Indeed, slides specifically alluded to glucose analysis though we did not get any details on the platform structure – Is it wireless? What devices and data streams does it support? According to Mr. Bergstrom, additional EU launches and a US launch are planned for the future though he did not share timing. All in all, it is fantastic to see Roche pushing forward on data and connectivity, and we’ll hope to get an update from the company when the ADA Exhibit Hall opens tomorrow.
• As he did in our interview last fall, Mr. Bergstrom noted that the next five years will be all about “acquisitions and roll-ups and partnerships and IPOs.” He stressed that industry is finally comfortable with the concept of digital health, which will allow companies in the near future to focus on collaboration and consolidations between large and small organizations. He identified the big entrants in the digital health space (Google, Qualcomm, Samsung, Apple) along with the large healthcare companies (biopharma, medtech), forecasting that the diversity of players is going to bring fantastic perspective to the field in the coming years.
• Mr. Bergstorm also spoke during his presentation about the potential of digital health solutions to “offload administrative burden.” In his ideal future, he suggested that digital heath solutions would allow clinicians to practice at the pinnacle of their abilities rather than getting “bogged down in things they are overqualified to be doing [e.g., paperwork, etc.].” He suggested that this is already done in other industries, noting that it isn’t a stretch to expect the diabetes field to catch up.

Pathway to Stop Diabetes Symposium

A high-powered group of researchers and industry representatives gathered in a closed session on Friday morning to hear presentations from the most recent recipients of the ADA’s Pathway to Stop Diabetes grants. Introductory remarks by ADA President Dr. Des Schatz and Dr. C. Ronald Kahn (Joslin Diabetes Center, Boston, MA) emphasized the program’s goals of promoting long-term, transformational change in diabetes care and encouraging collaboration. They also highlighted the selectiveness of the program: the 17 grant recipients selected thus far were chosen from a pool of 330 applicants, and as Dr. Kahn put it, “those 330 people were all pretty damn good.” The introductory speakers also noted that there was a concerted effort to focus attention on this program at this year’s ADA, with a dedicated poster session on Sunday and an oral presentation session on Monday in addition to this symposium. We remain very impressed with the Pathway initiative, which awards grants of up to $1.6 million over five to seven years to young diabetes researchers working on innovative projects focused on everything from neuronal regulation of feeding behavior to impaired wound healing. The program is supported by several heavy hitters in the diabetes industry, including Sanofi, Novo Nordisk, AstraZeneca, and Lilly, and we imagine this could make it easier for the researchers to eventually translate their findings into novel therapies. We think this program can play a major role in shaping the next generation of KOLs in diabetes. We also hope it can promote a more diverse group of leaders compared to the current crop (in a sign of some progress, 35% of the Pathway grant recipients are women compared to 26% of the mentors). See below for an more detailed overview of their work, though we unfortunately cannot provide specifics on the data presented at the symposium due to the closed nature of the session.

• Dr. Praveen Sethupathy (University of North Carolina, Chapel Hill, NC) is exploring links between obesity and the gut microbiome. His research aims to identify genetic factors that contribute to the intestine’s response to microbes under normal conditions and in obesity and diabetes. Due to the intestine’s crucial role in metabolism, Dr. Sethupathy is optimistic that this research could eventually reveal targets for future therapies.
• Dr. Zachary Knight (UCSF, San Francisco, CA) is investigating neuronal circuits that regulate food intake. While the field has a basic understanding of the mechanisms of weight regulation by the brain, Dr. Knight aims to delve deeper into the specific circuits that allow external cues to override normal regulation of feeding behavior. His research is focused on identifying the signals that activate the sensation of hunger and understanding how neural circuits promote food consumption. His goal is then to discover how these circuits are dysregulated in obesity, hopefully opening the door for new therapies.   
• Dr. Philip White (Duke University, Durham, NC) is using metabolomics to better understand the biochemical signatures of diabetes and obesity. As compared to lean mice, the metabolome of obese mice is characterized by a disequilibrium in levels of enzymes involved in the breakdown of keto-acids in the liver. Dr. White hypothesizes that restoring homeostasis among these enzymes could be an effective strategy for improving glucose and lipid metabolism.
• Dr. Andrew Scharenberg (Seattle Children’s Hospital, Seattle, WA) is using gene editing to engineer stable regulatory T cells (Tregs) in patients with type 1 diabetes. There is evidence suggesting that Treg dysfunction is one element of the immune imbalance in type 1 diabetes that leads to autoimmune attack on the beta cells. Dr. Scharenberg aims to edit genes in T cells to engineer Tregs that will remain stable and protect beta cells from autoimmune attack, potentially preventing or reversing type 1 diabetes. Dr. Jeffrey Bluestone (UCSF, San Francisco, CA) is currently furthest along in the Treg field with a therapy in phase 1 trials, but this approach (while at a much earlier stage) could potentially produce even more stable and robust cells with greater efficacy.
• Dr. Sui Wang (Harvard University, Boston, MA) is developing biological tools to dissect the gene regulatory networks (GRNs) mediating diabetic retinopathy. Dr. Wang is interested in understanding the unique roles of different retinal cell types, with particular emphasis on the molecular events underlying the disease’s early pathogenesis. She hopes that an understanding of these complex forces will leave researchers well-positioned to identify potential therapeutic targets to arrest the progression of retinopathy in its early stages.
• Dr. Daniel Ceradini (New York University, New York, NY) is investigating whether restoring a key antioxidant pathway can reverse the impaired tissue regeneration associated with diabetes. His research has previously demonstrated that this pathway is disrupted by hypoglycemia, and he aims to develop a therapy that can restore it and enable faster wound healing in people with diabetes. Wound healing is an area of particularly great unmet need in diabetes – the current standard of care consists of glycemic control and pressure off-loading – and we are very glad to see efforts to develop novel therapies.

Oral Presentations: Obesity and Related Conditions

Semaglutide Reduces Appetite and Energy Intake, Improves Control of Eating, and Provides Weight Loss in Subjects with Obesity

John Blundell, PhD (University of Leeds, UK)

Dr. John Blundell presented positive results on reductions in energy intake and appetite with once-weekly GLP-1 agonist semaglutide in people with obesity. This double-blind, crossover study examined the mechanisms of weight loss of semaglutide (dose-escalated to 1.0 mg) vs. placebo in 30 participants with obesity and without type 2 diabetes (baseline BMI of 34 kg/m²). At 12 weeks, the results found a reduction in body weight, with decreases in energy intake, appetite, and food intake along with overall improved control of eating. Specifically, findings demonstrated that ad libitum energy intake was lower with semaglutide vs. placebo at lunch (5 hours after standardized breakfast), evening meal, and snacks with relative reductions of 35%, 18%, and 22%, respectively. In addition, the semaglutide group achieved weight loss of 5 kg (with greater loss of fat mass compared to lean mass) vs. a small increase of 0.97 kg with placebo. Fasting overall appetite scores also indicated reduced appetite with semaglutide vs. placebo (p=0.0023), while nausea ratings were similar – suggesting that this effect was independent of side effects. Additionally, results from the overall appetite-suppression score and control of eating questionnaire indicated less cravings and greater control of eating. Notably, participants had greater reductions in energy intake of food groups of high fat and traditionally more “appealing” foods, which reflected the results from the Leeds food preference task. Dr. Blundell noted that the semaglutide group experienced a reduction in resting metabolic rate, but the difference was not statistically significant. These findings further confirm to us the impressive versatility of semaglutide, as the product has been suggested to be studied in several indications beyond type 2 diabetes, including NASH, obesity, and a range of macrovascular and microvascular complications – see more on this from our Novo Nordisk 1Q16 report. We have certainly seen significant enthusiasm for the GLP-1 agonist class within obesity – as already pioneered by Novo Nordisk’s Saxenda (liraglutide 3.0 mg) – and the eating behavior-specific findings from this study direct us back to potential mechanisms within the brain and its reward circuitry, which is marking itself as a fast growing area of research for obesity.

Questions and Answers

Q: Do you think the changes in resting metabolic rate are accounted for by the degree of weight loss?

A: Yes, when weight is lost rapidly, the body adjusts. It can drive appetite and make energy expenditure more efficient.

-- by Melissa An, Adam Brown, Abigail Dove, Helen Gao, Varun Iyengar, Emily Regier, Ava Runge, and Kelly Close