Obesity Highlights from the American Diabetes Association (ADA) 2025

Claudia Filozof, MD, PhD, VP. Therapeutic Head Fortrea

This year, the number of sessions in ADA covering obesity topics continued growing, focusing on higher-dose strategies with GLP1 agonists and dual, triple and tetra agonists as well as new therapeutic classes with complementary mode of action to incretins. The concept of improving the “quality of weight loss” with focus in fat loss continues gaining attention and new phase 2 data has been presented.

Across multiple late-breaking ADA presentations, investigators delivered pivotal data on once-monthly injectables, oral GLP-1 agonists, and novel co-agonist therapies, reporting clinically meaningful weight loss, improved glycemic outcomes, and good tolerability- safety profile in both people leaving with overweight or obesity with and without type 2 diabetes (T2D).

Several key obesity clinical trials presented significant findings:

MariTide clinical trial

The MariTide clinical trial, (once-monthly GLP-1 RA and GIP antagonist) led to 12%–16% average weight loss in adults with obesity and 8.4%–12% in those with T2D in the phase 2, 52-week trial. No plateau was observed, suggesting potential for further weight reduction. Improvements in cardiometabolic markers, including reductions in HbA1c, blood pressure, and lipids were also observed. However, rates of nausea and vomiting were very high across the MariTide arms, may be attributed to ascertainment bias with instrument used [Modified Index of Nausea, Vomiting, and Retching (M-INVR)], 25% of placebo participants reported nausea, as well. In the non-dose escalation arms, nausea was reported by 77-87% of participants, and vomiting was reported by 68-92% of participants. Results were simultaneously published in NEJM(1).

REDEFINE program

Data from the REDEFINE program highlighted that combined CagriSema (cagrilintide and semaglutide) therapy resulted in mean weight loss of 20.4% over 68 weeks in non-T2D adults (REDEFINE 1) and 13.7% in those with T2D (REDEFINE 2), significantly exceeding outcomes seen with either component alone or placebo. The combination also achieved improvements in glycemic control and metabolic biomarkers, while maintaining a safety profile consistent with GLP 1 and amylin therapies (2).

Phase 2 BELIEVE trial

The presentation of the phase 2 BELIEVE trial of bimagrumab and/or semaglutide in obesity without T2D raised high interest. Bimagrumab is a monoclonal antibody that blocks activin type II receptors, leading to increased muscle mass and decreased fat mass.

Overall, body weight reduction was greater with high dose combination, compared to high dose semaglutide. Additionally, combination therapy resulted in additive fat mass reduction, while preserving lean mass. More than 9-% of weight loss was attributable to fat mass reduction in all combination groups. Finally, the safety results were consistent with the known safety profiles of both bimagrumab and semaglutide, with no new safety signals during the extension treatment period.

Body weight reduction from baseline, was 2.5% with placebo, 9.7% with bimagrumab, 14.8% with semaglutide, and 20.2% with combination at week 48 with sustained weight loss at week 72 (19.8% with bimagrumab, 15.7% with semaglutide, and 22% with combination) (3).

SURMOUNT-5 trial

A post hoc analysis of SURMOUNT-5 trial (Tirzepatide compared with Semaglutide in patients living with obesity) suggests that rapid responders (i.e. those who reached ≥15% weight loss by Week 24) to any of these drugs lost more weight than non-rapid responders at week 72 but experienced slightly higher adverse events (4%-7%), especially hepatobiliary issue s(liver, gallbladder, and bile ducts). Rapid responders were more likely to be female and have lower weight at baseline. Dr. Aronne suggested that rapid response may not be necessarily “better”(4).

STEP-UP trial

The STEP-UP trial assessed a high dose semaglutide (7.2 mg) in patients with overweight or obesity without T2D. Assuming that all participants adhered to treatment, semaglutide 7.2 mg achieved weight loss of 20.7% at week 72, compared to 17.5% with semaglutide 2.4 mg and 2.4% with placebo (in the intention-to-treat population weight loss was 18.7% for semaglutide 7.2 mg vs 3.9% with placebo). Furthermore, one-third (33.2%) of people treated with semaglutide 7.2 mg achieved a weight loss of ≥25%, compared to 16.7% with semaglutide 2.4 mg and none with placebo. The safety and tolerability profiles were similar to those of semaglutide 2.4 mg(5).

Phase 3 SLIMMER trial

The Phase 3 SLIMMER trial, evaluated ecnoglutide, a novel GLP-1/glucagon receptor dual agonist, which showed significant weight loss benefits in adults with overweight or obesity. At 32 weeks, participants treated with ecnoglutide 2.4 mg once weekly achieved a mean weight reduction of 13.2%, compared to an increase of 0.1% in the placebo group. Ten participants did discontinue due to adverse events, which mostly consisted of mild-to-moderate gastrointestinal issues (6).

Phase 3 ACHIEVE-1 clinical trial

Additionally, Orforglipron phase 3 ACHIEVE-1 clinical trial in patients with Type 2 Diabetes and inadequate glycemic control with diet and exercise alone demonstrated up to 1.6% A1c reduction and weight loss ranging from 4.5% to 7.6% by week 40. The regimen was well tolerated, with mild-to-moderate GI side effects and no severe hypoglycemia or liver safety concerns. Results were simultaneously published in NEJM (7).

The Future of Obesity Treatment

The treatment of obesity is witnessing a paradigm change, as seen in ADA conference. This is fueled by the meteoric rise of GLP-1 agonist molecules leading to 2-digit weight loss and the new dual, triple and tetra agonist promising even higher weight reduction comparable to what it could be achieved in the past only by bariatric surgery. Effective obesity management in the future will require substantial weight loss along with improvement in fat distribution (reduction in visceral fat), cardiometabolic parameters, lean mass preservation and long-term weight maintenance. Last but not least, affordability and patient-centric delivery (oral pills, monthly autoinjectors, and long-term sustainability will be critical in this new era.

Learn more about our experience in advancing obesity drug development: https://www.fortrea.com/therapeutics/obesity

Reference list

• 1. Garvey, W. T., Wharton, S., Ryan, D. H., Weiss, T., Krempf, M., Jones, A., ... & Drucker, D. J. (2025). Once-monthly maridebart cafraglutide for the treatment of obesity. The New England Journal of Medicine, 390(22), 2025–2037.
• 2-6. Trials presented in: 85th Scientific Sessions of the American Diabetes Association; June 23, 2025; Chicago, Illinois.
• 7. Garvey, W. T., et al. (2025). Oral GLP-1 receptor agonist Orforglipron for T2D: Results from the Phase 3 ACHIEVE-1 Trial. The New England Journal of Medicine.