In insured US patients with overweight or obesity, ASCVD, and no diabetes, semaglutide was associated with fewer cardiovascular events than tirzepatide.
Evidence
A retrospective propensity-matched claims cohort included 10,625 semaglutide and 10,625 tirzepatide users aged at least 45 years and found lower rMACE-3 and rMACE-5 risks with semaglutide.
Caveat
Because this was an observational claims analysis, residual confounding and treatment discontinuation patterns may affect the comparison.
Simplified
AIMS: To assess the real-world effectiveness of semaglutide versus tirzepatide in reducing major adverse cardiovascular events (MACE) among patients with overweight/obesity and established atherosclerotic cardiovascular disease (ASCVD) without diabetes in an insured US population.
MATERIALS AND METHODS: This retrospective, observational cohort study used Komodo Research Data and included patients ≥45 years of age with overweight/obesity and ≥1 claim for myocardial infarction (MI), ischemic stroke, or peripheral artery disease first treated with semaglutide or tirzepatide between 13/5/2022-31/1/2025. Propensity score matching was used to balance key baseline characteristics between cohorts. Primary outcomes included (rMACE-3: MI, stroke, all-cause mortality) and (rMACE-5: rMACE-3, coronary revascularization, hospitalisation for heart failure). Cox proportional hazard models were used to compare time to first event for study outcomes. A secondary per-protocol analysis was conducted where patients were censored at treatment discontinuation (gap in therapy >30 days).
RESULTS: 10 625 patients were included in each matched cohort. Semaglutide was associated with statistically significant 29% (hazard ratio [HR] 0.71; p = 0.046) and 22% (HR 0.78; p = 0.040) reductions in the risk of rMACE-3 and rMACE-5, respectively, compared with tirzepatide. In the per-protocol analysis, semaglutide continued to be associated with a significantly lower risk of rMACE-3 (HR 0.43; p = 0.005) and rMACE-5 (HR 0.57; p = 0.003) compared with tirzepatide.
CONCLUSIONS: This real-world analysis of a large US claims database shows semaglutide was associated with early and significantly greater reductions in the risk of rMACE-3 and rMACE-5 versus tirzepatide among patients with overweight or obesity and ASCVD but without diabetes.
Key numbers
29%
Reduction in rMACE-3 Risk
Hazard ratio of 0.71 for rMACE-3.
22%
Reduction in rMACE-5 Risk
Hazard ratio of 0.78 for rMACE-5.
57%
Per-Protocol rMACE-3 Reduction
Hazard ratio of 0.43 in per-protocol analysis.
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