Comparison of cardiovascular outcomes between once‐weekly semaglutide and dulaglutide in adults with type 2 diabetes and established atherosclerotic cardiovascular disease in the United States

Abstract Aims This study aims to compare the risk of major adverse cardiovascular events (MACE) among United States individuals with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD) treated with once‐weekly semaglutide vs. dulaglutide. Materials and methods This was a retrospective cohort study using Optum's de‐identified Clinformatics Data Mart (Optum CDM) from 1 January 2007 through 30 September 2024. New initiators of semaglutide or dulaglutide ≥18 years with both T2D and ASCVD were included. The index date was the first date of a prescription claim for semaglutide or dulaglutide within the index medication identification period (1 January 2018 through 31 March 2024). The primary outcome was 3‐point MACE (stroke, myocardial infarction [MI], cardiovascular [CV]‐related death). Entropy balancing was applied to balance baseline characteristics. Weighted incidence rates per 1000 person‐years and doubly robust Cox proportional hazard ratios were reported. Results There were 75 243 enrolees included (semaglutide, 42 007; dulaglutide, 33 236). The mean age was 68.2 and 69.3 years (unweighted) in the semaglutide and dulaglutide cohorts, respectively. After balancing, standardized mean differences were <0.1 for all variables. The incidence rates of the primary outcome, 3‐point MACE, were 25.7 and 33.0 in the semaglutide and dulaglutide cohorts, respectively. Compared with the dulaglutide cohort, the semaglutide cohort had a 22% lower risk of 3‐point MACE (hazard ratio, 0.78 [95% CI, 0.70–0.87]; p < 0.001). Conclusions Among United States Medicare Optum CDM enrolees with T2D and ASCVD, semaglutide was associated with reduced risks of CV outcomes compared with dulaglutide. These results help to address an important evidence gap in selecting glucagon‐like peptide‐1 receptor agonists for this high‐risk population.