GLP1 receptor agonists in heart failure with preserved ejection fraction (HFpEF) – beyond weight loss: a condensed scientific review

More than half of cases of heart failure (HF) now occur with preserved ejection fraction (HFpEF), a heterogeneous syndrome strongly influenced by comorbidities such as obesity, hypertension, diabetes and atrial fibrillation. Despite recent evidence supporting SGLT2 inhibitors and mineralocorticoid receptor antagonists, morbidity and mortality remain substantial. GLP1 receptor agonists, initially developed for type 2 diabetes, induce profound weight loss and have demonstrated benefits across cardiovascular, renal and metabolic pathways relevant to HFpEF. Recent randomized controlled trials (RCTs) in obesity‑related HFpEF showed clinically meaningful improvements in symptoms, functional capacity and inflammatory biomarkers with semaglutide in STEP‑HFpEF, and a reduction in the composite of cardiovascular death or worsening HF events with tirzepatide in SUMMIT. Mechanistic evidence suggests effects on natriuresis, inflammation, cardiac remodelling, endothelial function and epicardial adipose tissue quality and volume. This review summarizes the pathophysiological rationale, clinical evidence, mechanistic insights and therapeutic positioning of GLP1 receptor agonists in HFpEF. Download the Plain Language Summary of this article: https://www.drugsincontext.com/plain-language-summaries/plain-language-summary-glp1-receptor-agonists-in-heart-failure-with-preserved-ejection-fraction-hfpef-beyond-weight-loss-a-condensed-scientific-review This article is part of the Real-world evidence on the use of GLP1 receptor agonists Special Issue: https://www.drugsincontext.com/special_issues/real-world-evidence-on-the-use-of-glp1-receptor-agonists