In people with type‑2 diabetes who had heart bypass surgery, the drug tirzepatide (which hits both GLP‑1 and GIP receptors) led to fewer strokes, heart attacks, deaths and hospital readmissions than the similar drug semaglutide. The benefits held up over three years and were strongest for brain‑related events and blood‑clot problems.

To compare the effectiveness of tirzepatide (a dual GLP-1/GIP receptor agonist) versus semaglutide (a GLP-1 receptor agonist) in improving postoperative outcomes among patients with type 2 diabetes mellitus (T2DM) undergoing coronary artery bypass grafting (CABG). We conducted a retrospective analysis using the TriNetX global research network, identifying 226,742 adults with T2DM who underwent isolated CABG between 2022 and 2024. Among these, 3,669 received tirzepatide and 19,521 received semaglutide. After 1:1 propensity score matching, 3,667 matched pairs were analyzed. Primary outcomes included cerebrovascular and cardiovascular events, postoperative complications, healthcare utilization, and all-cause mortality, assessed at 6-month and 3-year intervals. P-values were adjusted for multiple testing using the Benjamini-Hochberg procedure. Tirzepatide was associated with significantly lower risks of cerebrovascular events at both follow-up points, including reduced incidence of cerebrovascular disease (11.8% vs. 17.5%; HR = 0.831), cerebral infarction (4.6% vs. 7.3%; HR = 0.788), and cerebral occlusion without infarction (6.8% vs. 10.4%; HR = 0.838)-all of which remained statistically significant after multiple comparison correction (adjusted p = 0.0024). Cardiovascular outcomes also favored tirzepatide, with significant reductions in major adverse cardiovascular events (MACE) (39.7% vs. 49.5%; HR = 0.911), myocardial infarction (7.0% vs. 10.8%; HR = 0.838), and acute coronary disease (1.1% vs 2.3%; HR = 0.691); several of these remained significant after correction at both timepoints. While tirzepatide was associated with lower rates of surgical site infection, venous thrombosis, and CABG-specific complications, only venous thrombosis remained statistically significant after adjustment (adjusted p = 0.021). Additionally, tirzepatide users had reduced healthcare utilization and lower all-cause mortality, with 3-year readmission (16.4% vs. 23.4%; HR = 0.871) and mortality (1.9% vs. 4.7%; HR = 0.595) both remaining significant after adjustment (adjusted p = 0.002). Kaplan-Meier analysis confirmed sustained survival benefit. In patients with T2DM undergoing CABG, tirzepatide was associated with improved cerebrovascular and cardiovascular outcomes, reduced venous thrombotic complications, and lower long-term mortality and healthcare utilization compared to semaglutide. These findings support the therapeutic potential of dual GLP-1/GIP receptor agonism in high-risk post-CABG populations.