Superior Cerebrovascular Outcomes with Tirzepatide versus Semaglutide in Diabetic CABG patients: A Global Network Study of Propensity-Matched Patients

Abstract Purpose To compare the effectiveness of tirzepatide (dual GLP-1/GIP receptor agonist) versus semaglutide (GLP-1 receptor agonist) in managing post-operative outcomes for diabetic patients undergoing coronary artery bypass grafting (CABG). Methods Using the TriNetX global network (2022–2024), we analyzed 2,294 propensity-matched pairs of diabetic adults who underwent CABG and received either tirzepatide or semaglutide. Post-operative complications, cardiovascular events, cerebrovascular outcomes, healthcare utilization, and mortality at 6 months and 3 years were evaluated. Results At 3 years, tirzepatide showed superior cerebrovascular protection with reduced incidence of transient ischemic attacks (2.5% vs 3.6%, HR = 0.692, 95%CI = 0.494–0.970, p = 0.026) and cerebral infarction (5.6% vs 7.6%, HR = 0.739, 95%CI = 0.588–0.927, p = 0.006) compared to semaglutide. These benefits, however, were not present or significant in tirzepatide in the short term (6 months) and had similar risk rates to that of semaglutide. Despite tirzepatide’s long term cerebrovascular benefits, overall cardiovascular event rates were comparable between both cohorts. All-cause mortality between tirzepatide and semaglutide at 6 months and 3 years were also similar in risk. Post-operative complications and healthcare utilization were comparable between groups. Conclusion In diabetic patients undergoing CABG, tirzepatide demonstrated superior long term (3 year) cerebrovascular protection compared to semaglutide while maintaining a similar safety profile. These findings suggest tirzepatide may be particularly beneficial for preventing cerebrovascular events in this high-risk population.