SELECT Trial — Semaglutide 2.4 mg Cuts CV Events 20% (NEJM 2023)

SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity, Lincoff et al., NEJM 2023) was the landmark cardiovascular outcomes trial establishing that semaglutide directly reduces major adverse cardiovascular events (MACE) in obesity without diabetes — the first weight-loss medication to demonstrate this outcome. Trial design. A multinational, double-blind, placebo-controlled, phase 3 cardiovascular outcomes RCT (NCT03574597). Participants were randomized 1:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, in addition to standard cardiovascular care. Population. 17,604 adults with established cardiovascular disease (prior myocardial infarction, prior stroke, or symptomatic peripheral artery disease) and overweight or obesity (BMI ≥27 kg/m²), but without diabetes. Mean age 62 years; 72% men. Mean follow-up approximately 39.8 months (median ~3.3 years). Primary endpoint. Time to first MACE — defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Key results. MACE occurred in 6.5% of semaglutide-treated participants vs 8.0% on placebo (hazard ratio 0.80, 95% CI 0.72-0.90, p<0.001) — a 20% relative risk reduction. Mean weight change was -9.4% on semaglutide vs -0.9% on placebo. Improvements were also observed in cardiometabolic risk factors and inflammation markers. Adverse events. Gastrointestinal events were most common; semaglutide had more adverse-event-related discontinuations than placebo, but no excess of serious adverse events. Indian context. Cardiovascular disease is the leading cause of death in India and disproportionately affects South Asians at younger ages and lower body weights than Western populations. SELECT establishes a clinically meaningful CV benefit at the same 2.4 mg dose now available across multiple Indian generic brands. For Indian patients with prior cardiovascular events and overweight or obesity, semaglutide provides not only weight management but also direct cardiovascular protection.