American journal of preventive cardiologyJun 15, 2026

Semaglutide 2.4 mg and heart event risk in overweight or obese people without artery disease: The SCORE primary prevention study

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 16, 2026

Abstract

Semaglutide 2.4 mg is associated with lower risks of major adverse cardiovascular events (MACE) and heart failure outcomes.

A total of 48,184 individuals on semaglutide 2.4 mg were matched to 96,368 individuals not on the medication.
Semaglutide 2.4 mg was associated with a 41% reduction in the risk of revised 3-point MACE (HR: 0.59).
The risk of revised 5-point MACE was reduced by 35% with semaglutide 2.4 mg (HR: 0.65).
A 27% reduction in the risk of traditional 3-point MACE was observed (HR: 0.73).
The medication was linked to a 25% lower risk of traditional 5-point MACE (HR: 0.75).
Composite heart failure outcomes were also lower in patients taking semaglutide 2.4 mg over a mean follow-up of 9 months.

Simplified

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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;< 0.001), rMACE-5 (HR: 0.65;< 0.001), MACE-3 (HR: 0.73;< 0.01), MACE-5 (HR: 0.75;< 0.01), and composite HF outcomes over a mean follow-up of 9 months. p p p p

CONCLUSIONS: Semaglutide 2.4 mg was associated with lower risk of incident MACE and HF composite outcomes in this real-world study of patients with overweight/obesity without diabetes, who were at risk for developing ASCVD. Further research is warranted to confirm the role of semaglutide 2.4 mg in the primary prevention of ASCVD in this population.