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

📖 Top 30% JournalOct 22, 2025Current medical research and opinion

How GLP-1 Receptor Agonists Compare to Other Diabetes Medicines in Medicare Patients with Type 2 Diabetes and Heart Disease

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

OW GLP-1 RAs are associated with 18% lower risk of ischemic stroke compared to ONIGLTs.

OW GLP-1 RAs showed a 14% lower risk for myocardial infarction compared to ONIGLTs.
The risk of 2-point major adverse cardiovascular events (MACE) was 17% lower with OW GLP-1 RAs than with ONIGLTs.
A 28% lower risk for 3-point MACE was observed with OW GLP-1 RAs compared to ONIGLTs.
OW GLP-1 RAs demonstrated a 27% lower risk for 5-point MACE when compared to ONIGLTs.
Semaglutide specifically had a lower risk of cardiovascular outcomes compared to SGLT2is.

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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.

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