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Updated: May 26, 2025
Author Spotlight: Exploring the Relationship Between Lipotoxicity and HFpEF
Published on: March 29, 2024
Efficacy of GLP-1 Receptor Agonists in Patients With Heart Failure and Mildly Reduced or Preserved Ejection Fraction:
Saad Ahmed Waqas1, Muhammad Umer Sohail1, Muhammad Saad1
1Department of Medicine, Dow University of Health Sciences, Karachi, Pakistan.
Insights
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) significantly reduce worsening heart failure events in patients with heart failure with preserved ejection fraction (HFpEF). These findings suggest GLP-1RAs are a promising therapy for HFpEF, especially for those with obesity or diabetes.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Heart failure with preserved ejection fraction (HFpEF) constitutes over half of all heart failure cases.
- Obesity is a significant risk factor for HFpEF, and residual risk remains high despite current treatments.
- The role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in managing HFpEF is not well-established.
Purpose of the Study:
- To systematically review and meta-analyze the efficacy of GLP-1RAs in patients with HFpEF.
- To evaluate the impact of GLP-1RAs on cardiovascular death, worsening heart failure events, and their composite outcomes.
Main Methods:
- A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed.
- Included studies evaluated GLP-1RAs, including those in combination with glucose-dependent insulinotropic polypeptide (GIP).
- Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled using a random-effects model.
Main Results:
- Six RCTs involving 8788 patients were analyzed.
- GLP-1RAs significantly reduced the composite outcome of cardiovascular death or worsening HF events (HR: 0.68 [0.51-0.89]).
- A significant reduction was also observed for worsening HF events alone (HR: 0.56 [0.38-0.82]), but not for cardiovascular death alone (HR: 0.86 [0.67-1.12]).
Conclusions:
- GLP-1RAs effectively reduce worsening HF events and the composite of CV death or worsening HF in patients with HFpEF.
- The benefits are particularly notable in patients with obesity or diabetes.
- Further HFpEF-focused trials are warranted to confirm these promising findings.
Background:
Heart failure (HF) with mildly reduced or preserved ejection fraction (HFpEF) accounts for over half of cases of HF, with obesity playing a key role. Residual risk remains high despite available therapies. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown potential cardiometabolic benefits, but their role in HFpEF remains unclear.
Methods:
A systematic review and meta-analysis of randomized controlled trials evaluating GLP-1RAs in HFpEF were conducted. Studies evaluating GLP-1RA in combination with glucose-dependent insulinotropic polypeptide (GIP) were also included. The analyzed outcomes included cardiovascular (CV) death, worsening HF events and their composite. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by using a random-effects model.
Results:
Six randomized controlled trials involving 8788 patients were included. GLP-1RAs significantly reduced the composite outcome of CV death or worsening HF events (HR: 0.68 [0.51-0.89]; P = 0.006, I² = 47%) as well as worsening HF events alone (HR: 0.56 [0.38-0.82]; P = 0.003, I² = 51%). No significant reduction was observed for CV death alone (HR: 0.86 [0.67-1.12]; P = 0.27, I² = 0%).
Conclusion:
GLP-1RAs reduce worsening HF events and the composite of CV death or worsening HF in HFpEF, particularly in patients with obesity or diabetes. These findings support their role as a promising therapy requiring further HFpEF-focused trials.
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