The SELECT trial, published in the New England Journal of Medicine in November 2023, tested once-weekly subcutaneous semaglutide 2.4 mg against placebo in 17,604 adults aged 45 or older with established cardiovascular disease and a BMI of at least 27, but without diabetes. Participants were followed on top of standard cardiovascular care.
Major adverse cardiovascular events — cardiovascular death, non-fatal myocardial infarction or non-fatal stroke — occurred in 6.5% of the semaglutide group versus 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% with semaglutide versus −0.9% with placebo. Analyses suggested the cardiovascular benefit emerged early and was only partly explained by weight loss.
SELECT was the first demonstration that a drug approved for weight management reduces hard cardiovascular outcomes, and it supported an expanded US label for semaglutide (marketed for obesity as Wegovy) to reduce cardiovascular risk in this population.