Latest Developments in Diabetes and Obesity Therapies Take Center Stage at EASD 2025

The European Association for the Study of Diabetes (EASD) annual meeting, set to take place from September 15 to 19 in Vienna, Austria, promises to shed light on pivotal advancements in diabetes and obesity treatments. This year's conference comes at a crucial juncture, following several high-profile readouts that have reshaped the cardiometabolic landscape.

Orforglipron's Mixed Results and Safety Concerns

Eli Lilly's orforglipron, once hailed as the leading oral weight loss pill in development, has faced setbacks in its Phase III trials. While the drug outperformed placebo in reducing body weight for patients with overweight or obesity, with or without type 2 diabetes, its efficacy has been overshadowed by safety concerns.

Graig Suvannavejh, senior biotechnology and biopharmaceuticals analyst at Mizuho Securities, noted that the initial negative reaction to orforglipron's 72-week data from the ATTAIN-1 trial was primarily due to "surprisingly high levels of adverse events." Placebo-adjusted nausea rates increased significantly from 40 to 72 weeks across all dosages, with vomiting rates also rising over time.

"Usually the side effects for GLP-1s occur in the earlier stages of taking the drug," Suvannavejh explained. The late onset of toxicities "wouldn't be ideal if the goal was to take the pill as a maintenance therapy for the rest of your life."

Lilly is expected to present further data from the ATTAIN-1 trial at EASD, potentially providing more clarity on orforglipron's safety and tolerability profile.

Beyond Weight Loss: Cardiovascular Benefits of Incretin Therapies

While obesity treatments remain a focal point, EASD 2025 is set to explore the broader therapeutic potential of incretin therapies. Mihail Zilbermint, associate professor of Clinical Medicine at the Johns Hopkins School of Medicine, highlighted the importance of Novo Nordisk's SOUL trial on oral semaglutide and cardiovascular outcomes.

The SOUL trial, which tested the effects of Rybelsus (oral semaglutide) on major adverse cardiovascular events (MACE) in over 9,600 patients with type 2 diabetes, demonstrated a significant reduction in MACE. However, analysts have noted that the data were "complicated" and pointed to an "inconsistent benefit" across different MACE components.

EASD will feature several presentations on the SOUL trial, potentially clarifying its findings and implications. Zilbermint suggests that these results could set the stage for GLP-1 therapies to provide "long-term cardiometabolic protection in pill form."

This focus on cardiovascular benefits aligns with recent industry trends. Novo Nordisk's Phase III STEER trial, comparing injectable semaglutide to Eli Lilly's tirzepatide in patients with overweight or obesity and established cardiovascular disease, showed a 57% drop in MACE risk for semaglutide.

"Over the past year, incretin-based therapies have redefined what is possible, with benefits extending to weight loss, cardiometabolic risk reduction and more," Zilbermint noted. "We keep discovering new benefits."

As the pharmaceutical industry continues to explore the multifaceted potential of incretin therapies, EASD 2025 is poised to provide crucial insights into their safety profiles, efficacy beyond weight loss, and long-term cardiovascular benefits. The conference's outcomes may significantly influence the future direction of diabetes and obesity treatments, potentially reshaping patient care in the cardiometabolic space.