Key result
Semaglutide 2.4 mg linked to ~45% lower MACE risk in real-world ASCVD and obesity.
Why the study?
Does semaglutide 2.4 mg reduce the risk of major adverse cardiovascular events in individuals aged ≥45 years with ASCVD and overweight/obesity but without diabetes?
Cohort (n=27,963)
Does semaglutide 2.4 mg reduce the risk of major adverse cardiovascular events in individuals aged ≥45 years with ASCVD and overweight/obesity but without diabetes?
Hazard Ratio: 0.55
p-value: p=<0.001
In a real-world US cohort of patients with ASCVD and overweight/obesity without diabetes, initiation of semaglutide 2.4 mg was associated with a significantly lower risk of major adverse cardiovascular events.
AIMS: In this first interim analysis of the SCORE study, we investigated the risk of major adverse cardiovascular events (MACE) among individuals with atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity but without diabetes who initiated semaglutide 2.4 mg in real-world settings. MATERIALS AND METHODS: Individuals initiating semaglutide 2.4 mg aged ≥45 years with ASCVD and overweight/obesity but without diabetes were identified in a US database (01/01/2016-12/31/2023) and matched 1:2 to those not on semaglutide based on a non-parsimonious propensity-score model. 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 revascularisation, and hospitalisation for heart failure). Secondary outcomes included MACE-3 and MACE-5, defined similarly to rMACE-3 and rMACE-5 but replacing all-cause mortality with cardiovascular-related mortality. Exploratory outcomes included incident type 2 diabetes, major adverse kidney events, and major obesity-related adverse events. RESULTS: A total of 9321 individuals on semaglutide 2.4 mg were matched to 18,642 individuals not on semaglutide; patient characteristics were well-balanced between cohorts. Over a mean follow-up of 200 days, semaglutide 2.4 mg was associated with significantly lower risks of rMACE-5 (hazard ratio: 0.55; p < 0.001), rMACE-3 (0.43; p < 0.001), MACE-5 (0.65; p < 0.001), and MACE-3 (0.58; p < 0.01). Semaglutide 2.4 mg was also associated with lower risks of all-cause mortality, cardiovascular-related mortality, hospitalisation for heart failure, and all exploratory outcomes. CONCLUSIONS: In this real-world study of US individuals with ASCVD and overweight/obesity but without diabetes, semaglutide 2.4 mg was associated with significantly reduced risk of MACEs and other obesity-related morbidities (NCT06874751).
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Smolderen et al. (2025) conducted a cohort in Atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes (n=27,963). Semaglutide vs. Not on semaglutide was evaluated on Revised 3-point MACE (rMACE-3) and revised 5-point MACE (rMACE-5) (HR 0.55, p=<0.001). In real-world patients with ASCVD and overweight/obesity without diabetes, semaglutide 2.4 mg was associated with a significantly lower risk of revised 5-point MACE (HR 0.55; p<0.001).