The pharmacologic treatment of obesity is undergoing a significant transformation with the advent of GLP-1 receptor agonists and the development of novel therapies. These advancements promise substantial weight loss and improvements in associated comorbidities, marking a shift in how obesity is managed and perceived within the medical community.
Louis J. Aronne, MD, FACP, FTOS, DANOM, from Weill Cornell Medical College, highlighted the evolution of obesity pharmacotherapies at the Cardiometabolic Health Congress. He noted that while numerous obesity drug trials have been conducted over the past 35 years, only recently have treatments begun to demonstrate significant clinical impact.
Efficacy of GLP-1 Agonists
Semaglutide (Wegovy, Novo Nordisk) and tirzepatide (Zepbound, Eli Lilly) have demonstrated weight loss comparable to bariatric surgery, along with reductions in all-cause mortality, heart failure symptoms, chronic kidney disease progression, and diabetes risk. The demand for these drugs is so high that they have faced supply shortages, despite distribution limitations.
Emerging Therapies
Several new drugs are in later-stage trials, including the combined GLP-1/amylin analog cagrilintide/semaglutide (CagriSema, Novo Nordisk) and the triple GLP-1/GIP/glucagon agonist retatrutide (Eli Lilly). Phase 2 trial data for cagrilintide/semaglutide showed a mean weight loss of 15.6% and a 2.2% reduction in HbA1c in adults with obesity and type 2 diabetes. Retatrutide demonstrated even greater impact in its phase 2 trial, with patients experiencing a 24.2% reduction in body weight and improved HbA1c levels.
Obesity as a Primary Target
According to Aronne, obesity treatment is becoming more integrated into primary care, with a growing number of patients seeking weight loss interventions. He emphasized that weight loss can improve multiple comorbidities simultaneously, unlike treatments targeting individual conditions. For instance, achieving 15% or greater weight loss can lead to type 2 diabetes remission, reduced cardiovascular mortality, and improved heart failure.
Future Directions
Phase 3 data for cagrilintide/semaglutide and retatrutide are expected in 2026, potentially leading to FDA approval in 2027. As the treatment landscape expands, obesity is increasingly recognized as a disease requiring comprehensive management, similar to hypertension. The development of new drugs and therapeutic categories promises a brighter future for obesity treatment.
