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

Cardiovascular drugs and therapy2025PMID: 41317265

View on PubMed DOI: 10.1007/s10557-025-07820-z

Plain Language Summary

Researchers responded to criticism of their study finding that tirzepatide produced better brain and heart outcomes than semaglutide in diabetic patients who had heart bypass surgery. They defended the rigor of their analysis — which matched patients on over 40 characteristics — and noted that the brain blood vessel benefit was especially notable given that semaglutide showed no stroke benefit in a major trial. They argue their findings are hypothesis-generating for this under-studied high-risk patient group.

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.

Authors

Hussein, Mohammad H; Toraih, Eman A