Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta‐analysis
Authors' conclusion
In patients with HFpEF, GLP-1RA, SGLT2i and MRA significantly reduced the risk of cardiovascular death and HF hospitalisation, while GLP-1RA additionally improved the functional and quality-of-life outcomes. GLP-1RA and SGLT2i significantly reduced HF morbidity, and GLP-1RA uniquely improved functional status, positioning adiposity modulation as a central therapeutic target in HFpEF.
Study context
- Population
- Patients with heart failure with preserved ejection fraction (HFpEF) in RCTs of pharmacotherapies (ACE inhibitors, ARBs, beta blockers, mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, SGLT2is, GLP-1 RAs, nitrates and nitrites); PubMed, Embase, Cochrane Library to April 2025
- Participants
- 48,235 patients39 trials
- Comparison
- HFpEF pharmacotherapies vs placebo
- Outcome
- Composite of:
- CV death
- Heart failure (HF) hospitalisation
Methodological detailsfrequentist random-effects NMA
- Frequentist random-effects NMA
Pooled result
As reported in the abstract
CV death and HF hospitalisation
Each group vs placeboHazard ratio (95% CI)
GLP-1 RAs
0.73(0.61–0.88)
SGLT2isP-score: 0.807
0.79(0.70–0.90)
- GLP-1 RAs highest probability of ranking first (P-score)
- 0.871
Further pooled results
| Outcome | Estimate |
|---|---|
| 6MWT distanceGLP-1 RAs vs Placebo | mean difference +17.60 m (95% CI 8.53–26.67) |
| KCCQ-CSSGLP-1 RAs vs Placebo | mean difference +7.38 points (95% CI 5.51–9.26) |
- 6MWT distance: GLP-1 RAs elicited the greatest improvement
CV death and all-cause mortality
- No statistically significant differences among the treatments
Original publication
Comparative effectiveness of pharmacotherapy for heart failure with preserved ejection fraction: A systematic review and network meta‐analysis. Diabetes Obes Metab. Published 26 January 2026. doi:10.
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