BiomoleculesOct 29, 2025

GLP-1 Receptor Agonists and Their Role in Heart Failure

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 20, 2026

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve symptoms and promote weight loss in patients with heart failure with preserved ejection fraction (HFpEF).

GLP-1 RAs are associated with multiple biological pathways relevant to heart failure, including inflammation and oxidative stress.
These agents may influence sympathetic nervous system activity and cardiac metabolism, potentially impacting heart function.
Modulation of vascular pathways, such as nitric oxide signaling and endothelial function, is linked to improved blood flow and heart health.
Systemic metabolic and anti-inflammatory effects of GLP-1 RAs could provide a mechanistic basis for their clinical benefits in heart failure management.
While the direct cardiac effects of GLP-1 RAs remain unclear, their overall actions suggest a role in treating heart failure, particularly in metabolically driven cases.

Simplified

Heart failure (HF) is a growing public health concern, driven by the increasing prevalence of obesity, diabetes, and aging. Despite therapeutic advances, HF continues to be associated with high morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for glycemic control in type 2 diabetes, have demonstrated cardiovascular benefits in clinical trials. Recent studies, including STEP-HFpEF and SUMMIT, have shown improvement in symptoms and weight loss in patients with HF with preserved ejection fraction (HFpEF). GLP-1 RAs are involved in multiple biological pathways relevant to heart failure pathophysiology. These include pathways related to sympathetic nervous system activity, inflammatory cytokine signaling, oxidative stress, calcium handling, natriuretic peptide signaling, and cardiac metabolism. GLP-1 receptor agonists modulate vascular pathways involving nitric oxide signaling, endothelial function, and renal sodium handling, contributing to improved hemodynamics and neurohormonal balance. Together, these actions intersect with key neurohormonal and cellular processes contributing to chronic heart failure progression. This review explores the mechanistic overlap between GLP-1 receptor signaling and heart failure pathophysiology. This mechanistic overlap suggests a plausible role for these agents as adjunctive treatments in heart failure, especially in metabolically driven phenotypes. While direct cardiac effects remain incompletely defined, systemic metabolic and anti-inflammatory actions provide a mechanistic basis for observed clinical benefits.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

The authors declare no conflicts of interest.

PubMed

GLP-1 Receptor Agonists and Their Role in Heart Failure

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the glp-1 therapies brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the glp-1 therapies brief