Glucagon-like peptide-1-based incretin agonists in obesity-related heart failure with preserved ejection fraction: A systematic review and meta-analysis
Abstract
BACKGROUND
Obesity-related heart failure with preserved ejection fraction (HFpEF) is highly prevalent, symptomatically disabling, and lacks clearly disease-modifying pharmacotherapy. Glucagon-like peptide (GLP)-1-based incretin agonists-including GLP-1 receptor agonists (GLP-1 RAs; e.g. , semaglutide) and the dual GIP/GLP-1 RA tirzepatide-induce substantial weight loss and favorable cardiometabolic effects and have recently been evaluated in obese HFpEF populations.
AIM
To systematically evaluate the efficacy and safety of GLP-1–based incretin agonists (including GLP-1 RAs and the dual GIP/GLP-1 RA tirzepatide) in patients with obesity-related HFpEF and to quantify their effects through meta-analysis.
METHODS
PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, and Web of Science were searched from inception to October 2025 for randomized controlled trials (RCT) evaluating GLP-1–based incretin agonist therapy in adults with HFpEF and obesity. Outcomes included health status [Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS)], body weight, exercise capacity, heart failure events, and safety. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were performed for KCCQ-CSS and percentage body weight change.
RESULTS
Three RCTs (n = 1876) were included in quantitative synthesis: STEP-HFpEF (n = 529), STEP-HFpEF DM (n = 616), and SUMMIT (n = 731). GLP-1-based incretin agonist therapy significantly improved health status, with…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,876 participants or records.
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