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Background <p>Obesity-related heart failure with preserved ejection fraction (HFpEF) is characterized by impaired exercise tolerance and poor health status. Metabolic modulation using glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists has emerged as a potential therapeutic strategy.</p> Objectives <p>To evaluate effects of GLP-1 and GIP/GLP-1 agonists on heart failure hospitalization, symptoms, physical function, body weight, and mortality in patients with HFpEF and obesity.</p> Methods <p>We searched MEDLINE, CENTRAL, and ClinicalTrials.gov through November 2025 for randomized controlled trials enrolling adults with HFpEF (left ventricular ejection fraction ≥ 45%) and obesity (body mass index ≥ 30&#xa0;kg/m², or ≥ 27&#xa0;kg/m² with at least one obesity-related comorbidity) treated with GLP-1 or GLP-1/GIP agonists. Primary outcome was first heart failure hospitalization. Secondary outcomes included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, six-minute walk distance, percentage bodyweight change, and all-cause mortality.</p> Results <p>Four trials (<i>n</i> = 4,149) met criteria. Two trials contributed adjudicated first heart failure hospitalization, demonstrating pooled hazard ratio 0.52 (95% confidence interval 0.33–0.82). Incretin therapy improved Kansas City Cardiomyopathy Questionnaire by 7.4 (95% CI 4.9–9.9) points and six-minute walk distance by 17.6&#xa0;m (95% CI 10.7–24.5). Body weight decreased by -9.6% (95% CI -11.3 to -8.0). All-cause mortality did not differ significantly (hazard ratio 0.90, 95% confidence interval 0.67–1.22); however, given the limited number of events across available trials, this finding should be interpreted as inconclusive rather than indicative of a null mortality effect.</p> Conclusions <p>GLP-1-based and dual GIP/GLP-1 therapies improve symptoms, physical function, and weight and reduce heart failure events in adults with obesity-associated HFpEF, supporting metabolic modulation as a therapeutic approach.</p> Trial registration <p>Systematic review registration: CRD420251237462.</p>

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GLP-1 and dual GIP/GLP-1 agonists in obese patients with HFpEF: a systematic review and meta-analysis of RCTs

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月30日

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  • Elhaitham Yasir Awad Musa,
  • Amar Yasir Awad Musa

摘要

Background

Obesity-related heart failure with preserved ejection fraction (HFpEF) is characterized by impaired exercise tolerance and poor health status. Metabolic modulation using glucagon-like peptide-1 (GLP-1) receptor agonists and dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists has emerged as a potential therapeutic strategy.

Objectives

To evaluate effects of GLP-1 and GIP/GLP-1 agonists on heart failure hospitalization, symptoms, physical function, body weight, and mortality in patients with HFpEF and obesity.

Methods

We searched MEDLINE, CENTRAL, and ClinicalTrials.gov through November 2025 for randomized controlled trials enrolling adults with HFpEF (left ventricular ejection fraction ≥ 45%) and obesity (body mass index ≥ 30 kg/m², or ≥ 27 kg/m² with at least one obesity-related comorbidity) treated with GLP-1 or GLP-1/GIP agonists. Primary outcome was first heart failure hospitalization. Secondary outcomes included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score, six-minute walk distance, percentage bodyweight change, and all-cause mortality.

Results

Four trials (n = 4,149) met criteria. Two trials contributed adjudicated first heart failure hospitalization, demonstrating pooled hazard ratio 0.52 (95% confidence interval 0.33–0.82). Incretin therapy improved Kansas City Cardiomyopathy Questionnaire by 7.4 (95% CI 4.9–9.9) points and six-minute walk distance by 17.6 m (95% CI 10.7–24.5). Body weight decreased by -9.6% (95% CI -11.3 to -8.0). All-cause mortality did not differ significantly (hazard ratio 0.90, 95% confidence interval 0.67–1.22); however, given the limited number of events across available trials, this finding should be interpreted as inconclusive rather than indicative of a null mortality effect.

Conclusions

GLP-1-based and dual GIP/GLP-1 therapies improve symptoms, physical function, and weight and reduce heart failure events in adults with obesity-associated HFpEF, supporting metabolic modulation as a therapeutic approach.

Trial registration

Systematic review registration: CRD420251237462.