Glucagon-like peptide-1 receptor agonists for improving quality of life and mortality in adults with heart failure with preserved ejection fraction: A systematic review and meta-analysis of efficacy and safety

Nov 12, 2025Semergen

Glucagon-like peptide-1 receptor agonists and their effects on quality of life and survival in adults with heart failure with normal heart pumping

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Abstract

GLP-1 receptor agonists are associated with a 37% reduction in heart failure hospitalizations among patients with preserved ejection fraction.

The analysis included six randomized controlled trials and four observational studies, totaling 108,634 patients.
Major adverse cardiovascular events (MACE) were reduced with GLP-1RA therapy, presenting a hazard ratio of 0.73.
There was a significant improvement in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, with a mean difference of 8.55.
Patients experienced increased six-minute walk distance by an average of 15.90 meters with GLP-1RA treatment.
Gastrointestinal side effects were significantly higher in patients receiving GLP-1RA, with a relative risk of 1.56, while the risk of arrhythmias was lower at a relative risk of 0.84.

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AIM: Glucagon-like peptide-1 receptor agonists (GLP-1RA) may play a role in improving quality of life and improving long-term outcomes in heart failure with preserved ejection fraction (HFpEF) patients. We conducted a systematic review and meta-analysis evaluating the safety and efficacy of GLP-1RA in HFpEF patients.

METHODS: A systematic search strategy was developed using databases, namely PubMed, Web of Science, Cochrane, and Clinicaltrials.gov. The primary outcomes analyzed were hospitalisation events, MACE, and quality of life parameters, i.e., Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), 6-minute walk distance (6MWD). Review Manager and RStudio were employed for the statistical analysis, utilizing the random effects model with pre-defined effect measures.

RESULTS: We identified six randomized controlled trials (RCTs) and four observational studies in our meta-analysis, with a total of 108,634 patients. Hospitalization due to heart failure was reduced notably by 37% (HR 0.63; 95% CI: 0.54-0.72), and MACE events favoured GLP-1RA by HR of 0.73 (95% CI: 0.61-0.88; p=0.0008). We found a significant improvement with GLP-1RA therapy in KCCQ-CSS scores (MD 8.55, 95% CI: 6.78-10.29; p<0.00001) and 6MWD (MD 15.90, 95% CI: 15.35-16.46; p<0.00001). Regarding safety outcomes, a significant increase in GI effects (RR 1.56; 95% CI: 1.39-1.75; p<0.00001), and a lower risk of arrhythmias (RR 0.84; 95% CI: 0.79-0.90; p<0.0001).

CONCLUSION: GLP-1RA yields significant advantages in HFpEF patients, including enhanced quality of life, valuable weight loss, reduced heart biomarkers, and a decrease in heart failure hospitalizations. Regardless of elevated GI side effects, the GLP-1RAs act as encouraging therapeutic alternatives in HFpEF.

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Glucagon-like peptide-1 receptor agonists for improving quality of life and mortality in adults with heart failure with preserved ejection fraction: A systematic review and meta-analysis of efficacy and safety

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