The SELECT trial, published in the New England Journal of Medicine on November 11, 2023, established that semaglutide 2.4 mg reduces major adverse cardiovascular events by 20% in adults with overweight or obesity and established cardiovascular disease, independent of glycemic status.
The trial randomized 17,604 adults ≥ 45 years with BMI ≥ 27 and pre-existing CVD (but no diabetes) to semaglutide 2.4 mg or placebo for a median follow-up of 39.8 months. The primary composite endpoint (cardiovascular death, non-fatal MI, non-fatal stroke) occurred in 6.5% of the semaglutide group vs 8.0% of placebo (HR 0.80; 95% CI 0.72–0.90; p < 0.001).
In March 2024, the FDA expanded Wegovy's label to include cardiovascular risk reduction in adults with established CVD and overweight or obesity — the first weight-management drug to carry a CV-risk-reduction indication. The expanded label has substantially changed payer coverage discussions for semaglutide 2.4 mg in patients with documented CVD.