Glucagon-like peptide-1 receptor agonists in diabetic patients with heart failure with reduced ejection fraction - real world outcomes

Aims: To evaluate the effectiveness of GLP-1 RAs on clinical outcomes in diabetic patients with heart failure with reduced ejection fraction (HFrEF). Methods and results: In this retrospective observational cohort study, all adults with diabetes mellitus and HFrEF between 2014 and 2025 were identified. Patients treated with GLP-1 RAs were matched to controls using stratified exact matching. The primary outcome was a composite of heart failure hospitalization or all-cause mortality. Treatment effects were estimated using nonparametric bootstrap resampling (1,000 iterations) to derive risk ratios, NNT estimates, and corresponding 95% confidence intervals. Time-to-event analyses using Cox proportional hazards models were performed as a validation analysis. Among 7,878 patients with HFrEF, 793 (10.1%) patients who initiated GLP-1 RA therapy after HF diagnosis were matched to 1,825 controls. GLP-1 receptor agonist use was associated with a lower risk of heart failure hospitalization or death, with risk ratios of 0.58 (95% CI: 0.42-0.77) at 12 months and 0.72 (95% CI: 0.61-0.85) at 36 months. The combination of high baseline event rates and substantial relative risk reduction translated into remarkably low NNT values in the overall population, with an NNT of 17 (95% CI: 11-33) at 1 year and 13 (95% CI: 8-25) at 3 years. Post hoc subgroup analyses demonstrated consistent effects across clinical subgroups, with no significant heterogeneity observed. Conclusion: In this large real-world cohort of diabetic patients with HFrEF, GLP-1 receptor agonist therapy, in addition to guideline-directed medical therapy, was associated with a lower risk of death or heart failure hospitalization.