Association between semaglutide 2.4 mg and risk of cardiovascular events in people with overweight or obesity without atherosclerotic cardiovascular disease in the real-world: The SCORE – primary prevention study

Semaglutide 2.4 mg is approved for the secondary prevention of major adverse cardiovascular events (MACE) among individuals with overweight/obesity. We investigated its association with MACE among individuals with overweight/obesity without diabetes who had risk factors for atherosclerotic cardiovascular disease (ASCVD) in the real-world setting. Adults (≥45 years) with overweight/obesity and ≥3 risk factors for ASCVD but without diabetes were identified from a U.S. database (01/01/2016-12/31/2024). Patients initiating semaglutide 2.4 mg were propensity-score matched 1:2 to those not on semaglutide 2.4 mg. The primary outcomes included revised 3-point MACE (rMACE-3: myocardial infarction, stroke, and all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, coronary revascularization, and hospitalization for heart failure [HF]). Secondary outcomes included MACE-3 and MACE-5 (replacing all-cause mortality with cardiovascular-related mortality), and HF composite outcomes. A total of 48,184 individuals on semaglutide 2.4 mg were matched to 96,368 individuals not on semaglutide 2.4 mg; patient characteristics were well-balanced between cohorts. Semaglutide 2.4 mg was associated with lower risks of rMACE-3 (HR: 0.59; p