Comparative Effectiveness of Glucagon-like Peptide-1- Receptor Agonists in Patients With Heart Failure With Preserved or Minimally Reduced Ejection Fraction: A Comprehensive Bayesian Network Meta-Analysis and Network Meta-Regression

Jun 24, 2025Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

Comparing the effects of GLP-1 receptor drugs in heart failure patients with normal or slightly reduced heart pumping

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Abstract

In a network meta-analysis of 24,099 patients, semaglutide significantly reduced the risk of hospitalization for heart failure (HF) compared to placebo.

Semaglutide showed a 48% reduction in the risk of hospitalization for heart failure (HR 0.52, 95% credible interval [0.25, 0.87]).
Tirzepatide did not significantly impact hospitalization for heart failure (HR 0.51, 95% CrI [0.16, 1.24]).
Exenatide also did not significantly affect hospitalization for heart failure (HR 0.82, 95% CrI [0.33, 1.73]).
Semaglutide and exenatide reduced the risk of all-cause mortality, while tirzepatide did not.
Semaglutide was associated with improved 6-minute walk distance, while tirzepatide did not show this benefit.
Tirzepatide ranked highest for reducing hospitalization for heart failure and body weight, while semaglutide was ranked highest for decreasing cardiovascular mortality and improving the 6-minute walk distance.

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OBJECTIVES: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown beneficial effects on clinical outcomes in patients with heart failure (HF) with preserved ejection fraction (HFpEF) or minimally reduced ejection fraction (HFmrEF). This network meta-analysis (NMA) aimed to consolidate evidence from RCTs assessing the effects of GLP-1 RAs in HFpEF and HF with reduced ejection fraction.

METHODS: Several databases were searched comprehensively for relevant RCTs. A Bayesian NMA was conducted using R, and meta-regression was employed to investigate potential sources of heterogeneity. Statistical significance was evaluated using 95% credible intervals (CrIs) and surface under the cumulative ranking curve to rank treatment effectiveness. The primary outcome was hospitalization for HF (HHF).

RESULTS: Eight reports from 6 Phase 3 RCTs (N = 24 099), mostly with low risks of bias, were included. Compared to placebo, semaglutide reduced the risk of HHF (HR 0.52, 95% CrI [0.25, 0.87]), while tirzepatide (HR 0.51, 95% CrI [0.16, 1.24]) and exenatide (HR 0.82, 95% CrI [0.33, 1.73]) demonstrated no effect. Semaglutide and exenatide, but not tirzepatide, reduced the risk of all-cause mortality. None affected cardiovascular mortality. Semaglutide decreased the risk of worsening of HF events; tirzepatide did not. Tirzepatide and semaglutide enabled weight loss; however, only semaglutide notably enhanced the 6-minute walk distance. According to the surface under the cumulative ranking curve values, tirzepatide ranked highest for reducing HHF and body weight, semaglutide for decreasing cardiovascular mortality and worsening of HF events and improving the 6-minute walk distance, and exenatide for reducing all-cause mortality.

CONCLUSION: GLP-1 RAs provide significant benefits for patients with HFpEF or HFmrEF, with semaglutide offering more advantages than tirzepatide and exenatide.

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Comparative Effectiveness of Glucagon-like Peptide-1- Receptor Agonists in Patients With Heart Failure With Preserved or Minimally Reduced Ejection Fraction: A Comprehensive Bayesian Network Meta-Analysis and Network Meta-Regression

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