In a large-scale, multicenter trial, semaglutide, a glucagon-like peptide-1 receptor agonist, was evaluated for its ability to reduce cardiovascular risks in individuals with obesity or overweight but no diabetes. Participants, all aged 45 or older with existing cardiovascular disease and a BMI of at least 27, were randomized to receive a weekly 2.4 mg dose of semaglutide or a placebo. The primary goal was to determine if semaglutide could effectively lower the occurrence of major cardiovascular events, which included cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.

The trial enrolled 17,604 patients, split almost evenly between the semaglutide and placebo groups. Over an average follow-up of nearly 40 months and treatment duration of about 34 months, those receiving semaglutide experienced a lower rate of cardiovascular events (6.5%) compared to those on placebo (8.0%), achieving a hazard ratio of 0.80. Despite the positive outcomes, the semaglutide group had a higher rate of adverse events leading to discontinuation at 16.6%, significantly greater than the 8.2% in the placebo group. Thus, while semaglutide proved effective in reducing cardiovascular events among those with cardiovascular disease and obesity, it also led to increased adverse effects resulting in discontinuation of treatment.

Reference: Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Dec 14;389(24):2221-2232. doi: 10.1056/NEJMoa2307563. Epub 2023 Nov 11. PMID: 37952131.