Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction

Sep 13, 2024Heart failure reviews

Glucagon-like peptide-1 drugs as a possible treatment for heart failure with normal pumping function beyond just weight loss

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Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may significantly improve physical activity limitations and exercise capacity in obese patients with heart failure with preserved ejection fraction (HFpEF).

Obesity is a common phenotype associated with heart failure with preserved ejection fraction (HFpEF).
Multiple mechanisms link obesity to HFpEF, including sodium retention and low-grade systemic inflammation.
GLP-1 is a hormone that helps lower blood glucose levels by affecting insulin and glucagon secretion.
GLP-1 receptor agonists may contribute to cardioprotection by reducing epicardial fat and systemic inflammation.
The review discusses obesity's impact on HFpEF mechanisms and summarizes evidence on GLP-1 RAs' cardiovascular outcomes.

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Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various phenotypes, and obesity is one of the most common and clinically relevant phenotypes of HFpEF. Obesity contributes to HFpEF through multiple mechanisms, including sodium retention, neurohormonal dysregulation, altered energy substrate metabolism, expansion of visceral adipose tissue, and low-grade systemic inflammation. Glucagon-like peptide-1 (GLP-1) is a hormone in the incretin family. It is produced by specialized cells called neuroendocrine L cells located in the distal ileum and colon. GLP-1 reduces blood glucose levels by promoting glucose-dependent insulin secretion from pancreatic β cells, suppressing glucagon release from pancreatic α cells, and blocking hepatic gluconeogenesis. Recent evidence suggests that GLP-1 receptor agonists (GLP-1 RAs) can significantly improve physical activity limitations and exercise capacity in obese patients with HFpEF. The possible cardioprotective mechanisms of GLP-1 RAs include reducing epicardial fat tissue thickness, preventing activation of the renin-angiotensin-aldosterone system, improving myocardial energy metabolism, reducing systemic inflammation and cardiac oxidative stress, and delaying the progression of atherosclerosis. This review examines the impact of obesity on the underlying mechanisms of HFpEF, summarizes the trial data on cardiovascular outcomes of GLP-1 RAs in patients with type 2 diabetes mellitus, and highlights the potential cardioprotective mechanisms of GLP-1 RAs to give a pathophysiological and clinical rationale for using GLP-1 RAs in obese HFpEF patients.

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Beyond weight loss: the potential of glucagon-like peptide-1 receptor agonists for treating heart failure with preserved ejection fraction

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