GLP-1 drugs outperform SGLT2 inhibitors for cardiovascular protection in 119,000 Medicare patients with established heart disease | Research

The takeaway

Among 119,434 Medicare patients with T2D and ASCVD, once-weekly GLP-1 drugs reduced stroke 18%, MI 14%, 3-point MACE 28%, and 5-point MACE 27% versus other therapies, with semaglutide outperforming SGLT2i for all CV outcomes.

GLP-1 > SGLT2i for CV protection
Once-weekly GLP-1 drugs, especially semaglutide, reduced cardiovascular events 14-28% more than other therapies including SGLT2 inhibitors in 119,434 Medicare patients

What the researchers found

vs ONIGLTs: IS -18%, MI -14%, 2P-MACE -17%, 3P-MACE -28%, 5P-MACE -27%. vs SGLT2i: 2P-MACE -14%, 3P-MACE -15%, 5P-MACE -14%. Semaglutide: lowest risk vs SGLT2i for all outcomes. 41,835 GLP-1 + 77,599 ONIGLT matched patients.

Why it matters

This is the largest Medicare comparison showing GLP-1 drugs outperform even SGLT2 inhibitors for cardiovascular protection in established ASCVD—supporting GLP-1 drugs as first-choice for this high-risk population.

How the study worked

Observational cohort from Optum Medicare Advantage (2007-2024). Propensity score matching. 41,835 GLP-1RA + 77,599 ONIGLT. Incidence rates and time to first event.

What this study cannot tell us

Observational. Medicare population (≥65). US-specific. Propensity matching cannot eliminate all confounders. Early post-launch GLP-1 use may have selection bias.

How to read the evidence

Large propensity-matched observational study with 119,434 patients. Strong real-world evidence.

When this study was published

Published in 2025; data 2007-2024.

The bigger picture

This shifts the debate from "GLP-1 or SGLT2i?" toward "GLP-1 AND SGLT2i." While both are beneficial, GLP-1 drugs (especially semaglutide) show superior cardiovascular event reduction in established ASCVD.

Questions still open

Should all T2D+ASCVD patients start GLP-1 drugs before SGLT2i?
Why does semaglutide outperform other GLP-1 drugs and SGLT2i?
Would combination therapy provide additive protection?

Common questions

Which diabetes drug protects the heart best?

In this study of nearly 120,000 Medicare patients with established heart disease, GLP-1 drugs (especially semaglutide) outperformed all other diabetes medications including SGLT2 inhibitors for reducing heart attacks, strokes, and cardiovascular death. Semaglutide had the best outcomes across every cardiovascular endpoint.

Should I take a GLP-1 drug or an SGLT2 inhibitor?

Based on this study, GLP-1 drugs provide greater cardiovascular protection than SGLT2 inhibitors for patients with established heart disease. However, SGLT2 inhibitors have unique benefits for heart failure and kidney disease. Many patients may benefit from taking both, and your doctor can guide the choice based on your specific health needs.

Read the original research

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

Current medical research and opinion, 41(10), 1787-1798

View on PubMed ↗Publisher’s paper ↗

Citation

Tan, Xi; Liang, Yuanjie; Xie, Lin; Gutierrez, Cynthia; Harton, Joanna; Muhammad, Chalak; Swift, Caroline; de Havenon, Adam. (2025). Comparative effectiveness of GLP-1 RAs and other glucose-lowering therapies among Medicare Advantage beneficiaries with T2D and ASCVD.. Current medical research and opinion, 41(10), 1787-1798. https://doi.org/10.1080/03007995.2025.2577762