Summary
Glucagon-like peptide-1 (GLP-1) receptor agonists are associated with reduced cardiovascular risk in patients with diabetes.1 The Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial sought to understand whether patients without diabetes experience the same benefits from semaglutide.2
In this industry-sponsored, double-blind, placebo-controlled superiority trial, more than 17,000 patients with overweight or obesity who had preexisting cardiovascular disease without diabetes were randomized to placebo or once-weekly semaglutide (titration to 2.4 mg by 16 weeks). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
At 40 months of follow-up, semaglutide reduced the risk of cardiovascular events by 20%. A primary cardiovascular endpoint event occurred in 6.5% of the treatment group versus 8.0% of the placebo group (P < 0.001, hazard ratio: 0.8). Gastrointestinal side effects were significantly higher in patients in the treatment arm (16.6%) versus the placebo arm (8.2%) and were the most common reason for treatment discontinuation, though serious adverse events were similar in both groups.
Notably, the effects of semaglutide did not depend on baseline body mass index; participant weight loss on average was 9.4% from baseline. The lack of diversity of the trial limits general widespread applicability, with underrepresentation of women and patients from racial and ethnic minority groups.2,3
Sources
1Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653-662. doi:10.1016/S2213-8587(21)00203-5.
2Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563.
3Khera A, Powell-Wiley TM. SELECTing treatments for cardiovascular disease – obesity in the spotlight. N Engl J Med. 2023;389(24):2287-2288. doi:10.1056/nejme2312646.