Efficacy of GLP ‐1 receptor agonists in patients with obesity and heart failure with preserved ejection fraction: A systematic review and meta‐analysis of randomised controlled trials

🥉 Top 5% JournalSep 12, 2025Diabetes, obesity & metabolism

GLP-1 receptor agonists may help patients with obesity and heart failure with preserved pumping function: A review and combined analysis of clinical trials

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Abstract

GLP-1 receptor agonists significantly reduced heart failure events by 60% compared to placebo.

No significant differences were observed in cardiovascular mortality or all-cause mortality between GLP-1 RA and placebo groups.
Quality of life, as measured by the KCCQ-CSS score, improved by an average of 7.23 points with GLP-1 RAs.
Patients on GLP-1 RAs experienced a mean weight loss of 9.76 kg.
Functional capacity, assessed by the 6-minute walk distance, increased by 16.54 meters with GLP-1 RA treatment.
GLP-1 RAs were associated with an increased risk of drug discontinuation due to adverse events, primarily gastrointestinal issues.

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AIMS: Obesity increases the risk of heart failure with preserved ejection fraction (HFpEF). Glucagon-like-peptide-1 receptor agonists (GLP-1 RAs) appear to improve cardiovascular outcomes in these patients; however, this benefit remains uncertain.

MATERIALS AND METHODS: We performed a meta-analysis of randomised controlled trials (RCTs) assessing GLP-1 RAs in obese patients with HFpEF. Outcomes included all-cause and cardiovascular mortality, heart failure events, and quality of life. Embase, PubMed, and Cochrane were systematically searched. A random-effects model calculated risk ratios (RRs) or mean differences (MD) with 95% confidence intervals (CIs).

RESULTS: Three RCTs with a total of 1876 patients were included, of whom 50% (937) were randomised to GLP-1 RA and followed for a mean of 69.3 weeks. There was no difference between groups regarding cardiovascular mortality (RR: 0.79; 95% CI: 0.22-2.88; p = 0.72), all-cause mortality (RR: 0.98; 95% CI: 0.58-1.64; p = 0.93), or serious adverse events (RR: 0.66; 95% CI: 0.40-1.09; p = 0.10). However, compared to placebo, GLP-1 RAs significantly reduced heart failure events (RR: 0.40; 95% CI: 0.22-0.73; p = 0.003), improved quality of life (KCCQ-CSS mean difference [MD]: 7.23 points; 95% CI: 4.89-9.56), decreased body weight (MD: -9.76 kg; 95% CI: -13.50 to -6.01), and enhanced functional capacity (6MWD MD: 16.54 m; 95% CI: 10.18-22.91). Nonetheless, GLP-1 RAs increased the risk of drug discontinuation due to adverse events (RR: 2.36; 95% CI: 1.16-4.79; p = 0.02), primarily gastrointestinal (RR: 4.01; 95% CI: 2.15-7.45; p < 0.01).

CONCLUSIONS: GLP-1 RAs significantly reduced heart failure events, improved KCCQ-CSS score, reduced body weight, and improved 6MWD compared to placebo.

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