Obesity Takes Center Stage at Slimmed-Down Diabetes Meeting

Miriam E. Tucker

June 20, 2023

Obesity management will take center stage at this year's 4-day American Diabetes Association (ADA) 83rd Scientific Sessions, being held in San Diego, June 23-26, which is shorter by a day than prior meetings.

Of five major clinical trials to be presented, four involve obesity management and three evaluate incretin drugs specifically. These results will be reported more efficiently than in years past, as all symposia have been trimmed from 2 hours down to 90 minutes.

Also new in 2023 will be an opening keynote address, on Friday morning, by former National Institutes of Health (NIH) Director Francis Collins, MD, PhD, now a White House science advisor, an "innovation challenge" Saturday afternoon, and a plethora of debates scattered throughout the 4 days, totaling 17 in all. The debates will involve more audience interaction than in the past, complete with real-time polling.

"We've tried to be less didactic and more engaging...It's all geared towards a better educational experience," ADA Vice President, Research & Science Marlon Pragnell, PhD, told Medscape Medical News.

Indeed, Robert A. Gabbay, MD, PhD, agreed: "I think this will be a really exciting meeting with a lot of great content delivered in a more innovative way."

And much of that content will address obesity. "The really big theme, not just in the Scientific Sessions, but in the field in general, is obesity. There will be several really ...exciting presentations in that realm. I think there will be a lot of interest," noted Gabbay, who is ADA chief science & medical officer.

Obesity Management: Incretins, Surgery, and Lifestyle

On Friday afternoon, complete results of the 79-week randomized phase 3 SURMOUNT-2 trial of the twincretin tirzepatide (Mounjaro, Eli Lilly) for treating obesity or overweight in people with type 2 diabetes will be presented.

Top-line results for SURMOUNT-2 were released in April 2023, showing that tirzepatide achieved its primary weight-loss endpoints and key secondary endpoints, including A1c reduction.

The drug, a dual glucagon-like peptide-1 (GLP-1) agonist and glucose-dependent insulinotropic polypeptide (GIP) agonist, was approved by the US Food and Drug Administration (FDA) in 2022 for type 2 diabetes and is already being used off-label to treat obesity.

Previously, the results of SURMOUNT-1 had shown "unprecedented" weight loss with tirzepatide in people with obesity but without diabetes.

During the SURMOUNT-2 presentation, "We'll get a lot more information...There was some top-line suggestion that the weight loss wasn't as potent in people with diabetes as in those without, which is what we often see. But they'll drill down into the data...The dual agonist does seem to have added benefit," Gabbay commented.

Pragnell noted, "I suspect there will be some dramatic weight loss in type 2 diabetes as well."

On Sunday afternoon, data from two phase 3 trials of the oral formulation of the GLP-1 agonist semaglutide (Rybelsus, Novo Nordisk) will be presented.

OASIS 1 is a 68-week trial of weight loss in people with type 2 diabetes and overweight or obesity given once-daily 50-mg oral semaglutide, while PIONEER PLUS investigates different daily doses of oral semaglutide as a glucose-lowering agent in type 2 diabetes, with weight loss as a secondary endpoint.

"The key thing here is getting from injectable to oral," Pragnell told Medscape Medical News. "The ideal drug is something you can take as a tablet...A lot of work is going into incretin-like drugs with oral bioavailability...You want a drug with the most convenience for people so you get the best adherence."

The FDA approved the once-weekly subcutaneously injectable form of semaglutide for type 2 diabetes as Ozempic in 2017, oral semaglutide (Rybelsus) for type 2 diabetes in 2019, and once-weekly subcutaneous injectable semaglutide for obesity in adults as Wegovy in 2021. Wegovy was also approved for obesity for those aged 12 and over in the United States in 2022.

On Monday afternoon, phase 2 trial data will be presented for Lilly's novel GIP/GLP-1/glucagon receptor "triagonist," retatrutide, for treating obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD).

Results of a previous small 12-week, phase 1 study suggested that the triple agonist (then called LY3437943), might provide even more weight loss than currently approved incretin agents in people with type 2 diabetes.

"People are still learning about what incretins are doing. When you combine them it's interesting to see empirically how they work...Each has a different role and function. In combination, they may be additive or work differently...It's a very exciting area," Pragnell said.

Fittingly, this year's Banting Medal for Scientific Achievement will be awarded to Matthias H. Tschöp, MD, the German scientist whose pioneering work in gut hormones led to the development of the incretin drugs. He'll deliver the keynote Banting lecture on Sunday morning.

The fourth major piece of obesity research, the Alliance of Randomized Trials of Medicine vs Metabolic Surgery in Type 2 Diabetes (ARMMS-T2D) is a consortium of four studies designed to compare long-term efficacy and safety of surgery versus medical/lifestyle therapy on type 2 diabetes control and clinical outcomes.

Gabbay commented, "Bariatric surgery has been around a long time. It's quite effective and underutilized, given how big the problem is...It's going to be tough to beat bariatric surgery. Future studies will compare it with tirzepatide and other newer medications."

Cardiovascular Healthcare Delivery, DCCT Update

On Monday afternoon, results will be presented from COORDINATE on the effectiveness of a novel clinic-level educational intervention to improve the management of patients with type 2 diabetes and cardiovascular disease.

"It will be interesting. Improving care is not just creating new drugs but also improving how practices perform and how care is provided. ADA has disseminated the Standards of Care, and it's so important to see research on how best to implement that," Pragnell observed.

It's then the turn of type 1 diabetes to take the spotlight, in a special symposium that will provide new data on the impact of the landmark Diabetes Control and Complications Trial (DCCT) and its ongoing observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study, 40 years after DCCT's launch.

At a similar symposium held at the ADA meeting in 2013 to commemorate 30 years of DCCT, dramatic reductions in diabetes complications in participants with type 1 diabetes — achieved with intensive glycemic control — were still being seen.

Debates, With Audience Involvement

Type 1 diabetes management will also be addressed in at least three of the 17 planned debates, including one on Friday evening on do-it-yourself devices versus commercial closed-loop systems (artificial pancreas); technology versus immunomodulation on Saturday afternoon; and beta-cell replacement versus artificial pancreas on Monday afternoon.

Two debates will cover pregnancy-related topics, including use of low-carb diets and use of metformin during pregnancy in women with type 2 diabetes, both on Saturday.

Other hot-button debate topics will address initiation of combination therapy for type 2 diabetes on Friday morning, low-carb diets on Friday evening, and a "dual incretin duel" on Sunday afternoon.

Each debate speaker will give just a short argument, followed by back-and-forth and discussion involving the audience. With most debates, the audience will be polled at the beginning and at the end to see how many minds were changed.

"They're really interesting topics. We've tried to choose them so there's real debate, not a lopsided one where there's obviously just one side," Pragnell said.

Gabbay noted: "We realized we've been doing the same format since the 1980s. It hadn't changed that much. We really want to engage people more. What makes it special to go to a meeting versus reading the paper? It's an opportunity to interact, go back and forth, to have discussion."

Gabbay and Pragnell are ADA employees. They have reported no further disclosures.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in The Washington Post, NPR's Shots blog, and Diabetes Forecast magazine. She is on Twitter: @MiriamETucker.

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