Prognostic benefit of glucagon-like peptide-1 receptor agonists addition to sodium-glucose cotransporter 2 inhibitors in patients with atherosclerotic cardiovascular disease and heart failure: a cohort study

Abstract

Aims Managing patients with atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) is challenging. While sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) show cardiovascular benefits, the impact of combining these agents is unclear. This study evaluated whether adding GLP-1 RA to SGLT2i provides additional benefits in patients with both ASCVD and HF. Methods and results This retrospective observational study utilized the TriNetX database to analyse patients with ASCVD and HF who initiated GLP-1 RA with SGLT2i or SGLT2i alone from 1 August 2016 to 30 September 2024. A total of 2 797 317 patients were identified, with 96 051 patients meeting inclusion criteria. After propensity score matching, 5272 patients in each group were analysed. Primary outcomes included mortality or hospitalization within 1 year; secondary outcomes examined mortality, hospitalization, and heart failure exacerbation (HFE). Patients receiving GLP-1RA and SGLT2i therapies had significantly lower risk of mortality or hospitalization [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.74-0.83], mortality (HR 0.72; 95% CI 0.62-0.84), hospitalization (HR 0.78; 95% CI 0.73-0.83), and HFE (HR 0.77; 95% CI 0.72-0.83) vs. SGLT2i alone. Subgroup analyses showed consistent benefits in patients with HFpEF, HFrEF, patients with diabetes, obesity, chronic kidney disease, or those using semaglutide or dulaglutide, while liraglutide use showed a neutral effect. Drug-related side effects were monitored as safety outcomes, which showed no significant differences between groups. Conclusions In ASCVD and HF patients, adding GLP-1 RA to SGLT2i reduces 1-year mortality and hospitalization, warranting further investigation in diverse settings.