Incretin-based therapies for individuals with obesity and heart failure with mildly reduced or preserved ejection fraction: A systematic review and meta-analysis of randomized controlled trials
Abstract
Aims: Obesity is a major risk factor for heart failure with mildly reduced or preserved ejection fraction (HFpEF). This meta-analysis of randomised clinical trials (RCTs) evaluated the effects of incretin-based therapies (IBTs), including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GIP/GLP-1 RAs, on clinical outcomes in individuals with the obesity-HFpEF phenotype.
Materials and methods: A systematic search of PubMed, EMBASE and Web of Science through December 2024 identified RCTs comparing IBTs with placebo in patients with HFpEF and obesity. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled for binary outcomes, and estimated differences (EDs) for continuous outcomes, using an inverse variance random-effects model.
Results and conclusions: Six RCTs with 7282 participants (50.3% receiving IBTs) were included. IBTs reduced the risk of cardiovascular death or worsening HF (HR 0.74; 95% CI 0.63-0.88; I2 = 0%), worsening HF events (HR 0.62; 95% CI 0.47-0.81; I2 = 16%) and all-cause mortality (OR 0.81; 95% CI 0.67-0.99; I2 = 0%) compared to placebo. No significant difference was found in cardiovascular mortality alone. IBTs also improved quality of life, functional status, systolic blood pressure and weight loss in patients with obesity-HFpEF.
How strong is the evidence?
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: 7,282 participants or records.
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