Key result
Semaglutide 2.4 mg is linked to reduced MACE risk in real-world patients with ASCVD.
Why the study?
The association between semaglutide 2.4 mg and major adverse cardiovascular events among adults with clinical ASCVD and overweight/obesity without diabetes in real-world practice was not established.
Does semaglutide 2.4 mg reduce major adverse cardiovascular events in adults with clinical ASCVD and overweight/obesity without diabetes?
Cohort (n=114,923)
Does semaglutide 2.4 mg reduce major adverse cardiovascular events in adults with clinical ASCVD and overweight/obesity without diabetes?
Hazard Ratio: 0.55 (95% CI 0.47–0.65)
Real-world use of semaglutide 2.4 mg in patients with ASCVD and overweight/obesity without diabetes is associated with a significantly lower risk of cardiovascular events.
Supports semaglutide 2.4 mg in real-world clinical ASCVD; extends RCT evidence to routine practice.
AIMS: To evaluate the association between semaglutide 2.4 mg and major adverse cardiovascular events (MACE) among adults with clinical atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes in real-world clinical practice. MATERIALS AND METHODS: Adults aged ≥ 45 years with overweight/obesity and clinical ASCVD were identified from a United States database (2016-2024). Patients initiating semaglutide 2.4 mg were matched 1:2 with individuals not treated with semaglutide 2.4 mg through a propensity score model including > 70 demographic and clinical covariates. Primary outcomes were revised 3-point MACE (rMACE-3: myocardial infarction [MI], stroke, all-cause mortality) and revised 5-point MACE (rMACE-5: rMACE-3, heart failure [HF] hospitalisation, coronary revascularization). Secondary outcomes included 3-point MACE and 5-point MACE (replacing all-cause mortality with cardiovascular-related mortality) and HF composite outcomes; exploratory outcomes were incident type 2 diabetes (T2D), major adverse kidney events (MAKE) and major obesity-related adverse events (MORAE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: The final sample comprised 38 308 patients with semaglutide 2.4 mg use propensity-score matched to 76 615 patients without. Over a mean follow-up of 8.6 months, semaglutide 2.4 mg significantly reduced the risk of rMACE-3 (HR: 0.55; 95% CI: 0.47-0.65), rMACE-5 (0.63; 0.56-0.71), MACE-3 (0.66; 0.56-0.78) and MACE-5 (0.69; 0.62-0.77). Semaglutide 2.4 mg also significantly reduced the risk of HF composite outcomes, T2D, MAKE and MORAE. CONCLUSIONS: Semaglutide 2.4 mg was associated with a significantly reduced risk of MACE and other obesity-related outcomes, extending prior evidence of benefits to a broader clinical ASCVD population.
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Nanna et al. (2026) conducted a cohort in Clinical atherosclerotic cardiovascular disease (ASCVD) and overweight/obesity without diabetes (n=114,923). Semaglutide vs. Individuals not treated with semaglutide 2.4 mg was evaluated on Revised 3-point MACE (rMACE-3: myocardial infarction, stroke, all-cause mortality) (HR 0.55, 95% CI 0.47-0.65). Semaglutide 2.4 mg significantly reduced the risk of revised 3-point MACE (HR 0.55; 95% CI 0.47-0.65) and 5-point MACE (HR 0.63; 95% CI 0.56-0.71) in adults with ASCVD and overweight/obesity.
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