Comparing Cardiovascular Outcomes in New Users of Oral Semaglutide Versus Other Noninsulin Glucose-Lowering Therapies Among Adults with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease

INTRODUCTION: Clinical trials have found semaglutide reduces the risk of major adverse cardiovascular events (MACE) among people with type 2 diabetes (T2D) at high risk of MACE. Less is known about oral semaglutide's impact on real-world cardiovascular risk. METHODS: This observational cohort study used administrative claims data from Optum's deidentified Clinformatics® Data Mart Database to compare 3-, modified 3-, 5-, modified 5-, and 2-point MACE, ischemic stroke (IS), myocardial infarction (MI), and all-cause and cardiovascular-related death rates among people with T2D and atherosclerotic cardiovascular disease (ASCVD) who initiated oral semaglutide vs other noninsulin glucose-lowering therapies (ONIGLTs). Cardiovascular outcomes were compared between new users of oral semaglutide and propensity score-matched new users of dipeptidyl peptidase 4 inhibitors (DPP4is) or sodium-glucose cotransporter 2 inhibitors (SGLT2is). RESULTS: Oral semaglutide users (n = 10,878) had risk reductions of 17% and 21% in 3- and modified 3-point MACE, respectively, and significant risk reductions in 5-, modified 5-, and 2-point MACE, IS, and all-cause death vs ONIGLT users (n = 28,639). People who initiated oral semaglutide (n = 7218) had 22% and 24% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5- and modified 5-point MACE, IS, and all-cause death vs people who initiated DPP4is (n = 7218). Compared with SGLT2i users (n = 21,572), oral semaglutide users (n = 7491) had 21% and 22% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5-, modified 5-, and 2-point MACE. CONCLUSION: Consistent with clinical trial evidence, oral semaglutide was associated with a lower risk of cardiovascular outcomes among people with T2D and ASCVD in real-world settings.