Comparative Cardiovascular Outcomes of Tirzepatide and Glucagon‐Like Peptide‐1 Receptor Agonists in Patients With Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

BACKGROUND: To evaluate the association between tirzepatide use and 1-year risk of major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease, compared with GLP-1 (glucagon-like peptide-1) receptor agonists. METHODS: We conducted a retrospective, propensity score-matched cohort study using the TriNetX network. A total of 16 402 patients with type 2 diabetes and atherosclerotic cardiovascular disease initiating tirzepatide or GLP-1 receptor agonists between January 1, 2022, and March 31, 2025 were matched 1:1. The primary outcome was 1-year major adverse cardiovascular events; secondary outcomes included all-cause mortality, acute myocardial infarction, major adverse limb events, and tissue plasminogen activator use. RESULTS: Tirzepatide was associated with a lower risk of major adverse cardiovascular events (hazard ratio [HR], 0.75 [95% CI, 0.63-0.91]) and reduced risks of all-cause mortality (HR, 0.69 [95% CI, 0.53-0.90]), major adverse limb events (HR, 0.59 [95% CI, 0.39-0.88]), and acute myocardial infarction (HR, 0.70 [95% CI, 0.53-0.93]), compared with GLP-1 receptor agonists. Results were robust across subgroups and sensitivity analyses. CONCLUSIONS: Among patients with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide was associated with a significantly reduced 1-year risk of major adverse cardiovascular events and other cardiovascular outcomes compared with GLP-1 receptor agonists. These findings support the cardiometabolic potential of tirzepatide, warranting further prospective validation.