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

Background : The evidence regarding the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with heart failure with reduced ejection fraction (HFrEF) is limited and conflicting, with some studies suggesting a favorable effect and some not. The aim of the study was to examine the safety and efficacy of GLP-1 RA therapy in a large national database of patients with HFrEF. Methods : In this observational retrospective cohort, data was obtained from the electronic medical records of Clalit Health Services, the largest health care organization in Israel. Between the years 2014 -2024, using a 1:1 matching, patients with HFrEF who were treated with GLP-1 RA were compared with those who were not. Outcomes included heart failure (HF) hospitalization and death. A subgroup analysis by body mass index (BMI), age, sex, HbA1C level and concomitant medications was conducted as well. Results : Out of 22,411 patients with HFrEF, 3023 initiated GLP-1 RA therapy after the diagnosis of HF was made. After a 1:1 nearest-neighbor matching, 3858 patients were matched and included in the study, with 1939 and 1919 patients in the GLP-1 RA group and the control group, respectively. Mean age of the cohort was 69, 33% female, and mean BMI was 29.9 kg/m ² . While therapy with beta blockers and ACEI/ARB/ARNI was common within the cohort, only a third of the cohort was treated with SGLT2 inhibitors or mineralocorticoid receptor antagonists. Median follow-up time of the study was 30 months (17.06, 43.0). In a multivariable model which included multiple demographic and clinical variables, patients who were treated with GLP-1 RA were less likely to experience the primary outcome of death or HF hospitalization (HR 0.6, 0.53 – 0.68, p<0.001) compared with the control group. The subgroup analysis revealed a robust favorable effect of GLP-1 RA across the entire spectrum of patients with HFrEF. Conclusion : In this large cohort study of patients with HFrEF, GLP-1 RA therapy in addition to standard guideline directed medical therapy was associated with a lower rate of death and HF hospitalization. Future randomized trials are needed to confirm these results.