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

Publisher: Kluwer Academic Publishers Country of Publication: United States NLM ID: 9612481 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7322 (Electronic) Linking ISSN: 13824147 NLM ISO Abbreviation: Heart Fail Rev Subsets: MEDLINE

Original Publication: Norwell, MA : Kluwer Academic Publishers, c1996-

Heart Failure*/drug therapy ; Heart Failure*/physiopathology ; Heart Failure*/metabolism ; Glucagon-Like Peptide-1 Receptor*/agonists ; Stroke Volume*/physiology ; Stroke Volume*/drug effects ; Obesity*/drug therapy ; Obesity*/complications ; Obesity*/physiopathology; Humans ; Weight Loss ; Glucagon-Like Peptide 1/metabolism ; Incretins/therapeutic use ; Glucagon-Like Peptide-1 Receptor Agonists

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.
Competing Interests: Declarations. Ethical standards: The manuscript does not contain clinical studies or patient data. Consent for publication: All authors gave their consent for publication. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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Keywords: Cardiovascular outcome trials (CVOTs); Epicardial adipose tissue (EAT); Glucagon-like peptide-1 receptor agonists (GLP-1 RAs); Heart failure with preserved ejection fraction (HFpEF); Obesity; Systemic inflammation

0 (Glucagon-Like Peptide-1 Receptor)
89750-14-1 (Glucagon-Like Peptide 1)
0 (Incretins)
0 (Glucagon-Like Peptide-1 Receptor Agonists)

Date Created: 20240913 Date Completed: 20241214 Latest Revision: 20241214

20241215

10.1007/s10741-024-10438-2

39269643