Abstract
INTRODUCTION: Obesity is a global epidemic affecting 2.5 billion people and is recognized as the fourth leading cause of global mortality. Obesity is characterized by excessive accumulation of body fat and is associated with a range of health consequences, including an elevated risk of cardiovascular disease (CVD). Glucagon-like peptide-1 (GLP-1) receptor agonists have been proven to reduce cardiovascular outcomes in patients with diabetes. Study and results: The SELECT trial was a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial, conducted at 804 clinical sites in 41 countries. Patients were randomly assigned in a 1:1 ratio, to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo. The primary cardiovascular efficacy endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-first-event analysis. A total of 17,604 patients were recruited, with a mean age of 61.6 years and 72.3% males. The mean duration of exposure to semaglutide or placebo in the overall trial population was 34.2 ± 13.7 months. The primary CVD endpoint occurred in 6.5% (n = 569) of the semaglutide group and 8% (n = 701) in the placebo group (hazard ratio, 0.80; 95% CI, 0.72 to 0.90; P < 0.001). There was also a significant reduction of 9.39% in body weight among the patients taking semaglutide over 104 weeks after randomization versus 0.88% among the placebo group. CONCLUSIONS: Semaglutide reduces the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in obese and overweight non-diabetic patients with preexisting cardiovascular disease.