Semaglutide and tirzepatide effects on cardiovascular outcomes in people with overweight or obesity in the real world (STEER).

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 revised 3-point MACE (rMACE-3: MI, stroke, all-cause mortality) and revised 5-point MACE (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.