A recent observational study in diabetic patients who had heart bypass surgery found that tirzepatide, compared to semaglutide, was linked to lower risks of stroke, heart problems, blood clots, death, and fewer hospital visits. The researchers think this may be due to tirzepatide’s extra GIP‑receptor action, since semaglutide didn’t show a stroke benefit in other trials. The findings are preliminary but suggest tirzepatide could offer extra brain‑vascular protection in very high‑risk people.

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.