Glucagon-like Peptide-1 Receptor Agonists in Heart Failure: Mechanisms, Evidence and Identifying Optimal Candidates

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), established treatments for type 2 diabetes and obesity, exhibit cardiovascular benefits extending to heart failure (HF) with preserved ejection fraction (HFpEF). Mechanisms contributing to HF improvement include significant weight loss, blood pressure reduction, enhanced glycaemic control, anti-inflammatory effects and potential direct cardioprotective and vascular actions. Although cardiovascular outcome trials provided initial positive signals, dedicated HFpEF trials confirmed the efficacy of GLP-1RAs in HFpEF patients with obesity and/or diabetes. In some trials, GLP-1RAs significantly improved weight, symptoms of HF and HF events. Current evidence strongly supports GLP-1RAs in patients with HFpEF and obesity, with or without type 2 diabetes. The data do not support their use solely for HF with reduced ejection fraction.