Comparative 12–month Cardiometabolic: Impact of Semaglutide vs Tirzepatide: A Synthetic Propensity–matched Analysis

Background Objective deliver a 12–month, harmonized comparison of Semaglutide and Tirzepatide across three shared clinical domains: weight reduction, glycemic improvement, and cardiovascular risk reduction. Because individual patient data from original trials are not available, a synthetic cohort and propensity–score matching framework were used to approximate balanced treatment groups. Methods A simulated cohort (N=8000) was built using clinical variables aligned with SELECT (Semaglutide) and SUMMIT (Tirzepatide) populations: age, sex, BMI, type 2 diabetes status, cardiovascular disease history, HFpEF, eGFR, and systolic blood pressure. Treatment assignment followed a logistic model reflecting real–world prescribing patterns. Twelve–month cardiovascular events were generated using clinical predictors and a predefined treatment effect. Propensity scores were estimated via logistic regression and matched 1:1 using a caliper of 0.05. Standardized mean differences assessed balance. Outcomes included 12–month indexed reductions in weight, HbA1c, and composite cardiovascular risk. Results Matching produced acceptable balance (post–match SMD ‹0.1 for all covariates). In the matched cohorts, 12–month indexed outcomes showed: – Weight reduction: Semaglutide 10%, Tirzepatide 15% – HbA1c reduction: Semaglutide −1.6%, Tirzepatide −2.2% – Cardiovascular risk reduction (composite events): Semaglutide 16.8%, Tirzepatide 12.5% The simulation replicated expected patterns: stronger metabolic effects with Tirzepatide, more pronounced cardiovascular protection with Semaglutide. Conclusions A synthetic propensity–matched approach enables a unified 12–month comparison between the two agents, overcoming structural differences in the original trials. Results mirror broader clinical evidence: Tirzepatide delivers higher metabolic impact, while Semaglutide demonstrates stronger cardiovascular risk attenuation. The model is illustrative and not a substitute for analyses based on true patient–level data.