All-cause mortality and cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes and heart failure with reduced ejection fraction.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a popular first-line treatment option in managing Type 2 Diabetes Mellitus (T2DM) with cardiovascular co morbidities. Studies have established the benefit of GLP-1 RAs in improving cardiovascular (CV) outcomes in patients with T2DM. However, the impact of GLP-1 RAs on mortality and cardiovascular outcomes in patients with T2DM and Heart failure with reduced ejection fraction (HFrEF) remains uncertain. Methods: This retrospective cohort study employed an active-comparator new-user design using the TriNetX Research Network database. Patients aged 18 years or older with T2DM and left ventricular ejection fraction of ≤40 % were identified for inclusion. Patients were classified into two groups: GLP-1 RAs users versus dipeptidyl peptidase 4 inhibitor (DPP4i) users. Propensity score matching (1:1) was conducted based on demographics, body mass index, comorbidities, glycated hemoglobin levels, medications and socioeconomic factors resulting in a matched cohort of 26,196 patients. Outcomes analyzed included all-cause mortality, acute myocardial infarction, cerebrovascular accident, and all-cause hospitalization. Results: The GLP-1 RA user group demonstrated a reduced hazard ratio (HR, 95 % confidence interval) over 5 years compared with the DPP4i user group for all-cause mortality (0.62, 0.59-0.66, P < 0.001), all-cause hospitalization (0.71, 0.69-0.73, P < 0.001), acute myocardial infarction (0.87, 0.82-0.92, P < 0.001), heart failure exacerbation (0.83, 0.81-0.86, P < 0.001) and cerebrovascular accidents (0.85, 0.80-0.92, P < 0.001). Conclusion: In patients with T2DM and HFrEF, GLP-1 RA therapy shows potential beneficial effects in reducing CV events over 5 years compared to control (DPP4i) group.