GLP-1 based therapies reduce heart failure hospitalizations in HFpEF and CV mortality in younger HFrEF patients
Background
Despite advancements, heart failure (HF) remains a leading cause of morbidity and mortality, with distinct subtypes: preserved (HFpEF), mildly reduced (HFmrEF), and reduced (HFrEF) ejection fraction. Current pharmacotherapies often fall short, especially for HFpEF, which is frequently linked to obesity and metabolic dysfunction. Glucagon-like peptide-1 (GLP-1) based therapies, known for their cardiometabolic benefits, are being explored as novel treatments due to their potential cardioprotective effects beyond glycemic control.
Study Design
This systematic review and meta-analysis synthesized data from 14 randomized controlled trials (RCTs) involving 15,180 adult participants with heart failure. Researchers searched PubMed, Embase, Scopus, and trial registries until December 2025 for studies evaluating GLP-1 based therapies (including GLP-1 receptor agonists like tirzepatide) across the spectrum of left ventricular ejection fraction. Primary outcomes included heart failure hospitalizations (HFH), cardiovascular (CV), and all-cause mortality. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models, with subgroup analyses by HF subtype, age, and presence of coronary artery disease (CAD).
Results
The meta-analysis of 14 RCTs (totaling 15,180 participants) found that GLP-1 based therapies significantly reduced heart failure hospitalizations (HFH) with an overall relative risk of 0.84 (95% CI: 0.71-0.99). This benefit was particularly pronounced in HFpEF patients who also had stable coronary artery disease (CAD), showing a substantial reduction in HFH (RR: 0.61, 95% CI: 0.46-0.79). Limited data suggested a benefit for exenatide in HFmrEF patients, reducing HFH by 33% (RR: 0.67, 95% CI: 0.47-0.95).
Cardiovascular mortality was significantly reduced in HFrEF patients younger than 65 years old (RR: 0.71, 95% CI: 0.54-0.95). Composite outcomes of
HFHandCVmortality also showed a benefit for HFpEF patients, with a relative risk of 0.67 (95% CI: 0.54-0.83).
Key Findings
- GLP-1 based therapies reduced heart failure hospitalizations (HFH) by 16% overall (RR: 0.84, 95% CI: 0.71-0.99).
- HFH reduction was most significant in HFpEF patients with stable CAD (RR: 0.61, 95% CI: 0.46-0.79).
- Cardiovascular mortality decreased by 29% in HFrEF patients <65 years old (RR: 0.71, 95% CI: 0.54-0.95).
- Composite of HFH and CV mortality improved in HFpEF patients (RR: 0.67, 95% CI: 0.54-0.83).
- Limited data suggested exenatide reduced HFH by 33% in HFmrEF patients (RR: 0.67, 95% CI: 0.47-0.95).
Why It Matters
This meta-analysis provides compelling evidence that GLP-1 based therapies offer phenotype-specific benefits in heart failure, particularly for HFpEF and younger HFrEF patients. For peptide users and clinicians, this suggests that GLP-1 receptor agonists, including multi-agonists like tirzepatide, could be a valuable addition to existing HF management strategies, especially in patients with co-morbidities like obesity or CAD. While a usable protocol isn't directly provided by this meta-analysis, the findings strongly support the continued investigation and potential integration of these agents into clinical guidelines for specific HF subtypes. Consideration of GLP-1 based therapies for HFpEF patients with stable CAD, or younger HFrEF patients, may improve outcomes.
glp-1-agonist
tirzepatide
heart-failure
hfpef
hfmref
hfrf