Response To "Superior Cerebrovascular Outcomes with Tirzepatide Versus Semaglutide: A Call for Cautious Interpretation of Observational Data"

Abstract

We appreciate the thoughtful commentary by Drs. Dziewierz and Siudak regarding our study comparing tirzepatide versus semaglutide in post-CABG diabetic patients. While we acknowledge the inherent limitations of observational research, our propensity score matching achieved near-perfect balance across 40+ covariates (SMD = 0.033), including comprehensive medication proxies for diabetes control, lipid management, and blood pressure control. We observed consistent protective effects across multiple distinct outcome domains-cerebrovascular, cardiovascular, thrombotic, mortality, and healthcare utilization-with nine outcomes significant after Benjamini-Hochberg correction. The cerebrovascular benefit is particularly noteworthy given semaglutide's neutral stroke effect in SELECT trial, suggesting differential GIP receptor-mediated neurovascular protection. SURPASS-CVOT, comparing tirzepatide to dulaglutide (not semaglutide) in general ASCVD populations, addresses a different clinical question and may lack power for post-CABG subgroup analysis. Our findings provide hypothesis-generating evidence for an understudied high-risk population, warranting further investigation in dedicated trials.