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