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Semaglutide and Cardiovascular Outcomes in Obesity Without Diabetes

In the SELECT trial, subcutaneous semaglutide 2.4 mg once weekly produced superior outcomes compared with placebo in patients with preexisting cardiovascular disease and overweight or obesity but without diabetes. The primary cardiovascular outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.

Study participants were 45 years of age or older with preexisting cardiovascular disease and a BMI of 27 or greater and no history of diabetes. Using a double-blind, randomized, placebo-controlled, event-driven superiority trial design, participants received subcutaneous semaglutide 2.4 mg or placebo once weekly.

“A total of 17,604 patients were enrolled; 8,803 were assigned to receive semaglutide and 8,801 to receive placebo. The mean (±SD) duration of exposure to semaglutide or placebo was 34.2±13.7 months, and the mean duration of follow-up was 39.8±9.4 months. A primary cardiovascular end-point event occurred in 569 of the 8,803 patients (6.5%) in the semaglutide group and in 701 of the 8,801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P <0.001). Adverse events leading to permanent discontinuation of the trial product occurred in 1,461 patients (16.6%) in the semaglutide group and 718 patients (8.2%) in the placebo group (P <0.001).”

Editorial: “We are in a new era of treating obesity and cardiometabolic risk with a growing armamentarium of options,” editorialists write. “The SELECT trial provides evidence of improved cardiovascular disease outcomes with GLP-1 receptor agonists in the absence of diabetes. For patients with atherosclerotic cardiovascular disease and overweight or obesity, GLP-1 receptor agonist therapy with semaglutide joins the list of established therapies that form the basis of our pharmacologic strategies for reducing the risk of cardiovascular disease. However, we must continue to address the upstream underpinnings of obesity and the downstream effects on the communities that are the most vulnerable to the obesity epidemic and have the least access to these new treatment options.”

Source: New England Journal of Medicine