Key result
GLP-1 receptor agonists and tirzepatide show therapeutic promise across obesity-related HFpEF phenotypes.
Why the study?
HFpEF accounts for over half of all heart failure hospitalisations and is increasing in prevalence driven by obesity and T2DM, prompting a synthesis of recent trial evidence and mechanisms for GLP-1 RAs and tirzepatide in obesity-related HFpEF.
Do GLP-1 receptor agonists and tirzepatide improve symptoms and outcomes in patients with obesity-related HFpEF?
Do GLP-1 receptor agonists and tirzepatide improve symptoms and outcomes in patients with obesity-related HFpEF?
This review highlights GLP-1 receptor agonists and tirzepatide as promising therapeutic advances for obesity-related HFpEF, mediated by both weight-loss dependent and independent mechanisms, while noting open questions regarding non-obese HFpEF and HFrEF safety.
Answers are grounded in this paper and cite their sources.
May warrant consideration in obesity-related HFpEF; leaves open dedicated RCTs before practice change.
INTRODUCTION: Heart failure with preserved ejection fraction (HFpEF) accounts for over half of all heart failure hospitalisations and is increasing in prevalence, largely driven by obesity and Type 2 Diabetes Mellitus (T2DM). Glucagon-like-peptide receptor agonists (GLP-1 RAs) and the dual GLP-1/GIP agonist, tirzepatide, have been shown to be safe and effective medications in the treatment of T2DM and obesity as well as in obesity-related HFpEF. AREAS COVERED: This review summarises the pathophysiology of obesity-related HFpEF, mechanisms by which GLP-1 RAs and tirzepatide may improve symptoms and outcomes, and summarise evidence from recent randomised controlled and observational trials across the disease spectrum they have been studied in. Therapeutic implications and future research directions are also discussed. A structured literature search was performed using PubMed/MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) up to August 2025. EXPERT OPINION: GLP-1 receptor agonists and tirzepatide represent a promising therapeutic advance for obesity-related HFpEF. Benefits are likely mediated through weight loss dependent and weight-loss independent mechanisms. Important uncertainties remain regarding their role in non-obese HFpEF, optimal patient selection, and their safety in HFrEF.
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Chotalia et al. (2026) conducted a review in Obesity-related heart failure with preserved ejection fraction (HFpEF), obesity, and Type 2 Diabetes Mellitus. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and tirzepatide (dual GLP-1/GIP agonist) was evaluated. GLP-1 receptor agonists and tirzepatide represent a promising therapeutic advance for obesity-related HFpEF through weight-loss dependent and independent mechanisms.
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