Major adverse cardiovascular and limb events caused by tirzepatide in patients with type 2 diabetes at high cardiovascular risk: A comparison with sitagliptin.

AIMS: To elucidate the overall protective effects of tirzepatide against atherosclerosis-related events, including cardiovascular and lower-extremity events. METHODS: We conducted a retrospective cohort study using the TriNetX global health research network to identify patients with type 2 diabetes (T2D) who initiated tirzepatide or sitagliptin between January 2022 and December 2023. The primary outcome was major adverse cardiovascular and limb events (MACLE), defined as the composite of major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE: all-cause death and major lower extremity amputation). Propensity score matching was applied. RESULTS: After matching, 31,751 patients per group were analyzed. At 1 year, the incidence of MACLE was lower with tirzepatide compared to that with sitagliptin (4.3 % vs. 6.1 %; hazard ratio (HR), 0.70; 95 % confidence interval (CI), 0.66-0.76; p < 0.001). Tirzepatide was also associated with a reduced risk of MACE (HR, 0.71; 95 % CI, 0.66-0.76), MALE (HR, 0.39; 95 % CI, 0.34-0.46), and major lower extremity amputation (HR, 0.61; 95 % CI, 0.44-0.84). Consistent benefits were observed across major subgroups. CONCLUSIONS: Tirzepatide was associated with a significantly lower risk of cardiovascular and limb events compared to sitagliptin in patients with T2D.