Clin Res Cardiol. 2026 Jun 17. doi: 10.1007/s00392-026-02970-y. Online ahead of print.
ABSTRACT
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) both reduce cardiovascular events, but head-to-head comparisons for atrial fibrillation (AF), heart failure (HF), and ischemic stroke remain limited.
OBJECTIVE: We aimed to compare the incidence of new-onset AF, HF, and ischemic stroke among patients with T2DM treated with GLP-1RAs versus SGLT2i using a large, international real-world cohort.
METHODS: Using the TriNetX global network, adults aged 18-79 years with T2DM and without prior AF, HF, or ischemic stroke were identified. Patients receiving GLP-1RAs (n = 19,289) were propensity score-matched 1:1 with SGLT2i users (n = 19,289) based on age, sex, race, overweight or obesity, and hypertension. Outcomes were assessed from 90 to 1825 days after treatment initiation. Risk ratios (RRs) and hazard ratios (HRs) were calculated. Sensitivity analyses evaluated robustness.
RESULTS: GLP-1RA therapy was associated with lower risks of AF (RR = 0.61; HR = 0.57), HF (RR = 0.36; HR = 0.34), and ischemic stroke (RR = 0.79; HR = 0.75) compared with SGLT2i therapy. These associations remained generally consistent across multiple sensitivity analyses, including variations in follow-up periods and matching strategies.
CONCLUSION: In this large real-world cohort of patients with T2DM, GLP-1RA therapy was associated with lower risks of new-onset AF, HF, and ischemic stroke compared with SGLT2i therapy. These findings should be interpreted cautiously given the observational design and the potential for residual confounding, including confounding by indication. The findings are hypothesis-generating and may inform future prospective studies evaluating individualized cardiovascular risk reduction strategies.
PMID:42307748 | DOI:10.1007/s00392-026-02970-y