Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the management of type 2 diabetes and obesity due to their metabolic benefits. Beyond weight loss and glycemic control, emerging evidence suggests they may also exert cardioprotective effects. In the context of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF), GLP-1RAs have been associated with improvement in symptoms, physical capacity, biomarkers, and structural cardiac remodeling. These benefits appear to be independent of weight loss, suggesting additional mechanisms including anti-inflammatory effects, improved myocardial metabolism or modulation of epicardial adipose tissue. However, current data largely come from non-HF dedicated trials, with limited standardization of the HF phenotype. Results are overall inconsistent and may suggest potential harm in some cases, particularly in HF with reduced ejection fraction (HFrEF). This review aims to summarize the current evidence on the role of GLP-1RAs in heart failure, explore possible underlying mechanisms and highlight key gaps in knowledge.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the man-agement of type 2 diabetes and obesity due to their metabolic benefits. Beyond weight loss and glycemic control, emerging evidence suggests they may also exert cardiopro-tective effects. In the context of heart failure (HF), particularly HF with preserved ejection fraction (HFpEF), GLP-1RAs have been associated with improvement in symptoms, physical capacity, biomarkers and structural cardiac remodeling. These benefits appear to be independent of weight loss, suggesting additional mechanisms including an-ti-inflammatory effects, improved myocardial metabolism or modulation of epicardial adipose tissue. However, current data largely come from non-HF dedicated trials, with limited standardization of HF phenotype. Results are overall inconsistent and may suggest potential harm in some cases, particularly in HF with reduced ejection fraction (HFrEF). This review aims to summarize the current evidence on the role of GLP-1RAs in heart failure, explore possible underlying mechanisms and highlight key gaps in knowledge.