Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real‐world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World)

🥉 Top 5% JournalSep 10, 2025Diabetes, obesity & metabolism

Lower heart and blood vessel event risk in real-world patients starting semaglutide 2.4 mg

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Abstract

A total of 9321 individuals on semaglutide 2.4 mg were matched to 18,642 individuals not on semaglutide.

Semaglutide 2.4 mg was associated with a significantly lower risk of major adverse cardiovascular events, including a 55% reduction in the revised 5-point MACE.
The risk of the revised 3-point MACE was reduced by 57% among those using semaglutide.
Individuals on semaglutide showed a 35% lower risk of the 5-point MACE compared to those not on the medication.
A 42% reduction in the 3-point MACE was also observed in the semaglutide group.
Lower risks were noted for all-cause mortality and cardiovascular-related mortality in those treated with semaglutide.

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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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