ADA Highlights Innovations in Obesity Drug Therapies

At the American Diabetes Association (ADA) 84th Scientific Sessions held in Orlando, FL, new research presented in three studies highlighted significant advancements in drug therapies aimed at treating obesity. This research is critical as obesity remains a pressing health concern in the United States, impacting about 125 million people, including a substantial number of individuals with diabetes.

One of the significant findings involved HRS9531, a dual GLP-1/GIP receptor agonist tested in a Phase 2 study. This trial evaluated its effectiveness in obese adults without diabetes, showing promising results in reducing body weight, blood pressure, and blood glucose levels while maintaining a favorable safety profile. The study involved 249 Chinese adults with a body mass index (BMI) of 28-40 kg/m². Participants received weekly injections of HRS9531 at various doses (1.0 mg, 3.0 mg, 4.5 mg, and 6.0 mg) or a placebo for 24 weeks. The primary endpoint was the percentage change in body weight.

Results indicated significant weight loss in the HRS9531 groups compared to the placebo group. The weight reductions were 5.4%, 13.4%, 14.0%, and 16.8% across the different dosage groups, compared to just a 0.1% reduction in the placebo group. The majority of the participants achieved a weight reduction of 5% or more. The adverse events were mostly mild or moderate and included nausea, diarrhea, decreased appetite, and vomiting, particularly during dose escalation. Dr. Xiaoying Li, a senior author, emphasized the potential of HRS9531 for weight management, pointing out the ongoing Phase 3 study in Chinese individuals and plans for multi-regional studies.

Another noteworthy study, the Phase 2 MOMENTUM trial, assessed pemvidutide, a GLP-1/glucagon dual receptor agonist developed by Altimmune, for its weight loss effects in individuals with overweight and obesity. This randomized, placebo-controlled trial included 391 participants who were given pemvidutide at doses of 1.2, 1.8, or 2.4 mg or a placebo weekly for 48 weeks. The results were impressive, with those on the highest dose of pemvidutide losing an average of 15.6% of their total body weight. The treatment was well-tolerated, and significant reductions in serum lipids were observed, which can help mitigate cardiovascular risks. Additionally, a sub-study on body composition showed substantial preservation of lean mass, vital for maintaining physical function and reducing fracture risks. Dr. Louis J. Aronne highlighted the importance of such therapeutic approaches in managing obesity and its related conditions, indicating plans for larger Phase 3 trials.

Lastly, research on retatrutide, another agonist targeting GIP, GLP-1, and glucagon receptors, revealed that it could enhance insulin function and blood sugar control in individuals with type 2 diabetes. The study focused on biomarkers to understand how retatrutide impacts insulin-producing pancreatic beta cells and the body's insulin response. Results showed improvements in markers of beta-cell function and insulin sensitivity, along with reductions in markers of cellular stress and insulin resistance. Dr. Melissa K. Thomas underscored the need for new medications to simplify diabetes treatment regimens and improve blood sugar management. Several Phase 3 trials are underway to further explore retatrutide's effectiveness and safety in individuals with type 2 diabetes and obesity.

These studies collectively highlight significant progress in developing effective treatments for obesity and diabetes, offering new hope for better health outcomes and improved quality of life for affected individuals.

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