Comparison of cardiovascular outcomes in patients with diabetes treated with tirzepatide versus semaglutide: a multi-institutional analysis

Abstract Introduction Glucagon-like-peptide-1 (GLP-1) receptor agonists have been demonstrated to have cardiovascular benefits in patients with diabetes. Two of the most prescribed medications in this class are tirzepatide and semaglutide. Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist, while semaglutide is a selective GLP-1 receptor agonist. Tirzepatide and semaglutide have previously been directly compared to assess efficacy in glycemic control as the primary endpoint. However, there is limited data directly comparing cardiovascular outcomes between the two medications in patients with diabetes. This retrospective cohort study compares the incidence of major adverse cardiovascular events (MACE) in patients with diabetes treated with tirzepatide or semaglutide. Purpose The purpose of this study is to identify differences in cardiovascular outcomes between patients with diabetes treated with tirzepatide as compared to semaglutide. Materials and Methods The TriNetX research network was used for this study. Two patient cohorts were generated using International Classification of Disease 10 (ICD-10) codes and medication codes in the TriNetX system. Both cohorts of patients had a history of diabetes (E08-E13) and no prior history of cerebral vascular accident (I63) or myocardial infarction (I21). One cohort received semaglutide and the other tirzepatide. Each cohort was prohibited from receiving the other agent. The cohorts were balanced for age, race, gender, and ethnicity by propensity score matching and the greedy nearest neighbor algorithm resulting in 36,212 patients in each arm. They were then evaluated for the 3-year outcomes of major adverse cardiovascular events (myocardial infarction, cerebral vascular accident, and death). Results Tirzepatide was associated with statistically significantly fewer MACE outcomes compared to semaglutide for each of the individual endpoints as well as the overall composite endpoint over the 3 year follow up period. Table 1. MACE events for semaglutide and tirzepatide. Table 2. Relative risks for semaglutide MACE endpoints compared to tirzepatide. Conclusions In this retrospective cohort study, tirzepatide was associated with a lower incidence of major adverse cardiovascular events compared to semaglutide in patients with diabetes. These findings suggest that tirzepatide offers superior cardiovascular protection for primary prevention compared to semaglutide and warrant further investigation in future studies and clinical trials.Table 1Table 2