Abstract
Introduction and Objective: Glucagon-like peptide-1 receptor agonist (GLP-1RA) agents have demonstrated cardiovascular disease (CVD) benefits in adults with type 2 diabetes (T2D) at high and moderate CVD risk. However, their head-to-head comparative risk of cardiovascular outcomes is unknown.
Methods: We conducted a clinical trial emulation comparing CVD outcomes between patients treated with four GLP-1RAs. Using medical and pharmacy claims data from commercial, Medicare Advantage, and traditional Medicare plans between 2019-2021 for adults ≥21 years with T2D and moderate CVD risk (estimated 1-5% annualized risk of a major cardiovascular event [MACE: myocardial infarction, stroke, or death]) who initiated dulaglutide, exenatide, liraglutide, or semaglutide, we used propensity score inverse probability of treatment weighted Cox proportional hazards models to compare the hazard of MACE, expanded MACE (MACE plus heart failure hospitalization or arterial revascularization), each component of expanded MACE, and hospital/emergency department visits for hypoglycemia.
Results: We identified 36,656 patients initiating dulaglutide (mean age 64.5 ± 8.5 years, 46.8% male), 4,530 initiating exenatide (64.7 ± 8.2 years, 47.3% male), 9,794 initiating liraglutide (64.7 ± 8.3 years, 45.4% male), and 34,163 initiating semaglutide (64.4 ± 8.5 years, 46.6% male). Compared to dulaglutide, semaglutide was associated with lower hazard of MACE (HR 0.86, 95% CI 0.80-0.94), expanded MACE (HR 0.92, 95% CI 0.88-0.97), death (HR 0.84, 95% CI 0.74-0.94), stroke (HR 0.84, 95% CI 0.72-0.99), and arterial revascularization (HR 0.93, 95% CI 0.88-0.99). Liraglutide was associated with a lower hazard of death when compared to dulaglutide (HR 0.77, 95% CI 0.63-0.95).
Conclusion: Semaglutide may be the GLP-1RA associated with the greatest cardiovascular risk reduction in patients with T2D at moderate CVD risk.