Cardiovascular Outcomes in Patients with Type 2 Diabetes and Heart Failure with Reduced Ejection using Glucagon-like Peptide-1 Receptor Agonists

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RA) improve cardiovascular outcomes in patients with type 2 diabetes (T2D) and obesity, and more recently they have been shown to be beneficial in patients with obesity and heart failure with preserved ejection fraction. Their role in patients with heart failure and reduced ejection fraction (HFrEF) and T2D remains underexplored. Methods: A retrospective cohort study was conducted using data pooled from the TriNetX platform. Patients with T2D and HFrEF who were initiated on GLP1-RA therapy during the period May-13-2026 to Jun-6-2026 were identified. One:one propensity-score matching with controls was performed. Time-to-event analysis was conducted to compare the one-year incidences of all-cause mortality and a primary composite outcome of acute myocardial infarction, ischemic stroke and acute heart failure, between the two matched-cohorts. Secondary outcomes included individual components of the primary composite outcome and any inhospital encounter. Results: Two well-matched cohorts with 38,879 patients in each were formed. Patients treated with GLP1-RAs had a lower incidence of all-cause mortality (4.2% vs. 12%; absolute risk difference [ARD] -7.8, 95% CI -8.17 to -7.41; HR 0.4, 95% CI 0.34[boxh]0.38) and the primary composite outcome (32.5% vs. 48.3%; ARD -15.8, 95% CI -16.47 to -15.11; HR 0.6, 95% CI 0.57[boxh]0.60) compared to the control group. The GLP1-RA group were also at lower risk of all secondary outcomes compared to the control group. Conclusion: In a real-world study, GLP1-RA therapy was associated with lower risk of all-cause mortality and cardiovascular outcomes in patients with T2D and HFrEF.