Comparative effectiveness of GLP-1 RAs and other glucose-lowering therapies among Medicare Advantage beneficiaries with T2D and ASCVD.

OBJECTIVE: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended as glucose-lowering therapies for people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). Real-world evidence is limited comparing cardiovascular (CV) outcomes between once-weekly (OW) GLP-1 RAs vs other non-insulin glucose lowering therapies (ONIGLTs) including SGLT2is. This study aimed to compare CV outcomes among Medicare Advantage (MA) beneficiaries with T2D and ASCVD initiating OW GLP-1 RAs or ONIGLTs. METHODS: This observational cohort study included MA beneficiaries with T2D and ASCVD within Optum's de-identified Clinformatics Data Mart Database (01/2007-03/2024). Propensity score matching was used to compare adults initiating OW GLP-1 RAs or ONIGLTs. Incidence rates and time to the first event of ischemic stroke (IS), myocardial infarction (MI), 2-, 3-, and 5-point major adverse cardiovascular event (MACE) during follow-up were assessed. Individual OW GLP-1 RAs were compared with SGLT2is. RESULTS: Post-matching, 41,835 adults were treated with OW GLP-1 RAs and 77,599 with ONIGLTs. Compared with ONIGLTs, OW GLP-1 RAs had 18% lower risk for IS, 14% lower for MI, 17% lower for 2-point MACE, 28% lower for 3-point MACE, and 27% lower for 5-point MACE. Compared with SGLT2is, OW GLP-1 RAs had 14% lower risk of 2-point MACE, 15% lower risk of 3-point MACE, and 14% lower risk of 5-point MACE. Semaglutide had lower risk of all CV outcomes vs SGLT2is. CONCLUSION: Among MA beneficiaries with T2D and ASCVD, risk of CV outcomes was lower with OW GLP-1 RAs, particularly semaglutide, vs ONIGLTs including SGLT2is.