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

Abstract 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.