Adults with type 2 diabetes mellitus (T2DM) and established atherosclerotic cardiovascular disease (ASCVD) remain at elevated risk for major cardiovascular events. Comparative cardiovascular outcomes among newer incretin-based therapies are therefore clinically relevant. An analysis published in Diabetes Care evaluated cardiovascular outcomes among adults with T2DM and ASCVD who initiated tirzepatide compared with dulaglutide or semaglutide in routine clinical practice.
The study used two target trial emulations that included commercially insured adults who initiated subcutaneous tirzepatide, dulaglutide, or semaglutide between June 2022 and December 2024. The primary outcome was modified major adverse cardiovascular events (MACE), defined as a composite of nonfatal myocardial infarction, nonfatal stroke, and all-cause death. In the first analysis, new users of tirzepatide and dulaglutide were matched one to one using propensity scores. A second analysis used the same matching approach to compare tirzepatide with semaglutide. Incidence rates per 1,000 person-years and hazard ratios were calculated.
After matching, the tirzepatide–dulaglutide comparison included 9,233 pairs and the tirzepatide-semaglutide comparison included 25,266 pairs. Modified MACE occurred less frequently among tirzepatide initiators than dulaglutide initiators, with incidence rates of 31.3 and 39.4 per 1,000 person-years, respectively (HR 0.80; 95% CI 0.65-0.99). Lower all-cause mortality was also observed among tirzepatide initiators compared with dulaglutide initiators (HR 0.60; 95% CI 0.43-0.83). Post hoc analyses also identified fewer pneumonia-related hospitalizations among tirzepatide initiators than dulaglutide initiators.
In the comparison between tirzepatide and semaglutide, modified MACE incidence rates were similar. Rates were 23.7 per 1,000 person-years among tirzepatide initiators and 23.2 per 1,000 person-years among semaglutide initiators (HR 1.03; 95% CI 0.90-1.17). Overall, the analysis showed lower modified MACE rates with tirzepatide than dulaglutide. Modified MACE rates were similar between tirzepatide and semaglutide.
