Next-Generation Obesity Treatments Take Center Stage at ADA 2025

The American Diabetes Association's 2025 Scientific Sessions have shed light on the evolving landscape of obesity treatments, with pharmaceutical companies unveiling promising data for novel therapies aimed at addressing the limitations of current weight loss medications. The conference highlighted a shift towards more targeted approaches, focusing on muscle preservation, reduced side effects, and innovative mechanisms of action.

Muscle Preservation: A Key Focus for Future Therapies

Eli Lilly's bimagrumab, an antibody targeting activin/myostatin type II receptors, has shown promising results in preserving muscle mass during weight loss. In the Phase IIb BELIEVE trial, bimagrumab combined with Novo Nordisk's semaglutide led to a 22.1% reduction in body weight at 72 weeks, with 92.8% of the weight loss attributed to fat reduction. This data positions bimagrumab as a potential complementary treatment to existing GLP-1 agonists.

Similarly, Scholar Rock's apitegromab, which targets myostatin, demonstrated a nearly 55% muscle preservation advantage when used in combination with Eli Lilly's tirzepatide. The Phase II EMBRAZE trial showed that patients treated with both apitegromab and tirzepatide lost 3.4 lbs of lean mass over 24 weeks, compared to 7.6 lbs in those given tirzepatide alone.

Novel Mechanisms and Combination Therapies

Novo Nordisk is advancing its next-generation amylin analog, amycretin, which targets both GLP-1 and amylin receptors. After 36 weeks of treatment, patients experienced a 24.3% reduction in weight, showcasing the potential of dual-action therapies in the obesity space.

Zealand Pharma introduced dapiglutide, a potentially first-in-class drug activating both GLP-1 and GLP-2 receptors. This unique mechanism aims to address not only weight loss but also underlying inflammation associated with obesity. Phase Ib data revealed an 11.6% weight loss over 28 weeks, with potential benefits for adjacent conditions such as cardiovascular disease and liver disease.

Terns Pharmaceuticals is exploring a different pathway with TERN-501, a thyroid hormone receptor-beta (THR-β) agonist. Preclinical data suggest that when combined with semaglutide, TERN-501 can elicit greater weight loss compared to semaglutide alone, primarily through fat mass reduction.

Market Dynamics and Future Outlook

The obesity treatment market is projected to reach $150 billion annually by the early 2030s, driving intense competition among pharmaceutical companies. While GLP-1 agonists like Novo Nordisk's Wegovy and Eli Lilly's Zepbound have shown significant efficacy, the focus is now shifting towards addressing their limitations, such as muscle loss and gastrointestinal side effects.

Industry experts emphasize the need for more patient-friendly treatments that prioritize ease of use, accessibility, and muscle preservation. As the field evolves, combination therapies and novel mechanisms of action are expected to play crucial roles in shaping the future of obesity treatment.