The effects of tirzepatide and semaglutide on clinical and metabolic outcomes in patients with heart failure with preserved ejection fraction and obesity: a systematic review and meta-analysis
In brief
Incretin agonists cut worsening heart-failure events by half in obese HFpEF
In three randomized trials of nearly 1,900 patients, semaglutide or tirzepatide lowered the risk of worsening heart-failure events by about 55% and boosted quality-of-life scores by roughly seven points while adding 17 m to six-minute walk distance. The drugs also produced modest weight loss and were generally well tolerated, but larger long-term trials are still needed.
- Journal
- Nutrition, metabolism, and cardiovascular diseases : NMCD (Q1)
- Published
- 8 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Ahmed J AlAraibi, Fatema Naser Shakeeb, Tasneem Alqatta, Abu-Baker Sharafeldin, Laura Dempsey, Alexandra E Butler
- PMID
- 42772984
- DOI
- 10.1016/j.numecd.2026.104994
Why clinicians should know about it
- Picked for Family Practice (top studies of the week, 27 September 2026): GLP‑1 agonists in HFpEF, specialist cardiology trial
- Picked for Cardiology and Cardiovascular Medicine (top studies of the week, 27 September 2026): HFpEF tirzepatide meta-analysis improves therapy
- Picked for Epidemiology (top studies of the week, 27 September 2026): Systematic review of drug efficacy, not population study
Abstract
BACKGROUND AND AIMS: Heart failure with preserved ejection fraction (HFpEF) with obesity remains a therapeutic challenge with limited options. Glucagon-like peptide-1 (GLP-1) receptor agonists and dual incretin agonists may improve health status, functional capacity, and metabolic parameters. We evaluated the efficacy and safety of semaglutide and tirzepatide in this population. METHODS AND RESULTS: We searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to June 2025. Mean differences (continuous outcomes) and risk ratios (worsening heart-failure events) were pooled using random-effects models; other outcomes were synthesised narratively. Four studies met the HFpEF-specific criteria (three randomized trials and one observational cohort); the primary analysis was restricted to the three randomized trials (n = 1876), with SELECT and FLOW retained as indirect supportive evidence. Semaglutide or tirzepatide improved KCCQ-CSS (+7.39 points; 95% CI 5.43-9.35) and 6-min walk distance (+17.18 m; 11.82-22.54), and reduced worsening heart-failure events (risk ratio 0.45; 0.31-0.66). Body weight decreased by -7.73% (-10.70 to -4.76; I2 = 93%). Findings were robust in sensitivity analysis; secondary outcomes showed consistent CRP and HbA1c reductions; gastrointestinal intolerance was the most common adverse event. CONCLUSIONS: Semaglutide and tirzepatide were associated with improvements in health status, functional capacity, and body weight, and fewer worsening heart-failure events, in HFpEF with obesity, with an acceptable safety profile. They may have an adjunctive role, although larger, longer-term dedicated outcome trials are needed.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.