Heart failure & cardiomyopathiesMeta-analysis
Effect of Glucagon-Like Peptide-1 Receptor Agonists on Heart Failure Outcomes and Cardiovascular Death Across Varying Cardiovascular-Kidney-Metabolic Comorbidity
- Systematic review and meta-analysis of randomised trials
- random-effects models
Authors' conclusion
Glucagon-like peptide-1 receptor agonists reduce HFH and CV death across CKM conditions, with generally consistent effects in varying combinations of these diseases. The potential exception is among patients with HFrEF, where a reduction in risk of CV death, but a numeric increase in HFH, was observed.
Study context
- Population
- Patients with heart failure (HF), T2DM, chronic kidney disease (CKD), obesity and combinations of these diseases (primary and secondary analyses of GLP-1RA clinical outcome trials)
- Participants
- 87,549 patients · 15 trials
- Comparison
- GLP-1 receptor agonists vs placebo
- Outcome
- Composite of:
- HF hospitalization
- CV death
Pooled result
As reported in the abstract
Composite HFH/CV death, by cardiovascular-kidney-metabolic (CKM) condition
GLP-1RAs vs PlaceboHazard ratio (95% CI)
HF
0.81(0.69–0.96)
T2DM
0.85(0.78–0.93)
obesity
0.70(0.58–0.86)
CKD (non-significant)
0.79(0.61–1.01)
Further pooled results
| Outcome | HR (95% CI) | |
|---|---|---|
| First HF hospitalization, by CKM condition — GLP-1RAs vs Placebo · T2DM | 0.89 (0.80–0.99) | |
| First HF hospitalization, by CKM condition — GLP-1RAs vs Placebo · obesity | 0.63 (0.45–0.87) | |
| First HF hospitalization, by CKM condition — GLP-1RAs vs Placebo · HF (non-significant) | 0.85 (0.69–1.04) | |
| First HF hospitalization, by CKM condition — GLP-1RAs vs Placebo · CKD (non-significant) | 0.82 (0.64–1.06) | |
| CV death, by CKM condition — GLP-1RAs vs Placebo · HF | 0.88 (0.77–0.99) | |
| CV death, by CKM condition — GLP-1RAs vs Placebo · obesity | 0.83 (0.73–0.93) | |
| CV death, by CKM condition — GLP-1RAs vs Placebo · CKD (non-significant) | 0.80 (0.60–1.08) | |
| HFrEF (subgroup): HFH and CV death — GLP-1RAs vs Placebo · HFH (non-significant increase) | 1.17 (0.93–1.47) | |
| HFrEF (subgroup): HFH and CV death — GLP-1RAs vs Placebo · CV death | 0.67 (0.50–0.90) | |
| 0.512Hazard ratio (log scale) |
HF with reduced ejection fraction (HFrEF) (subgroup): Heart failure hospitalization (HFH) and cardiovascular (CV) death
- Effects consistent across subgroups, except HFrEF
Safety
| Outcome | RR (95% CI) | |
|---|---|---|
| Serious adverse events · not associated with increased risk | 0.94 (0.89–1.00) | |
| 0.512Relative risk (log scale) |
Original publication
Effect of Glucagon-Like Peptide-1 Receptor Agonists on Heart Failure Outcomes and Cardiovascular Death Across Varying Cardiovascular-Kidney-Metabolic Comorbidity. Eur J Heart Fail. Published 22 September 2025. doi:10.1002/ejhf.70048
Summarised from the published abstract; every number is checked against it