OBJECTIVE: Randomized clinical trials show that subcutaneous semaglutide is modestly superior to dulaglutide in reducing HbA1c and body weight, but no trial has compared their effectiveness on hard cardiovascular outcomes. This study aimed to examine whether semaglutide and dulaglutide differ in cardiovascular effectiveness.
RESEARCH DESIGN AND METHODS: This new-user, active-comparator cohort study used nationwide population-based Danish healthcare data to emulate a target trial of adults with type 2 diabetes receiving standard care who initiated subcutaneous semaglutide compared with dulaglutide. Up to five semaglutide initiators were matched to one dulaglutide initiator on a propensity score estimated from 52 variables. The outcome was a major adverse cardiovascular event (MACE), including myocardial infarction, ischemic stroke, heart failure, coronary revascularization, and cardiovascular death. In per-protocol analyses, Aalen-Johansen estimates were used to calculate risks, risk differences, and risk ratios at 3 years, accounting for informative censoring at nonadherence to the assigned treatment via time-varying inverse probability of censoring weights.
RESULTS: The semaglutide group included 2535 individuals, and the dulaglutide group 569 (median age [IQR], 61 [52-71] years; 1105 female individuals [36%]). Within 3 years, the risk of MACE was 6.0% (95% CI, 4.5%-7.8%) in the semaglutide group and 6.2% (95% CI, 4.0%-8.9%) in the dulaglutide group, corresponding to a risk difference of -0.2% (95% CI, -3.2% to 2.8%) and a risk ratio of 0.97 (95% CI, 0.59-1.61).
CONCLUSIONS: This target trial emulation did not provide evidence for a substantial difference in cardiovascular outcomes between individuals with type 2 diabetes initiating semaglutide and dulaglutide.