Incretin-Based Therapies in Obesity-Related Heart Failure With Preserved Ejection Fraction (HFpEF): A Systematic Review of Emerging Cardiometabolic Disease Modification Beyond Glycemic Control
- Design
- Systematic review · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Synthesis of studies conducted predominantly in people with obesity/overweight.
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 2[Auto] Systematic review/meta-analysis of randomized trials (auto-provisional; heterogeneity and included-study quality not assessed).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; last sentences of abstract] Collectively, the current evidence supports the growing role of incretin-based therapies as promising phenotype-oriented interventions in obesity-related HFpEF and raises the possibility that targeted cardiometabolic modulation may influence multiple domains of disease pathophysiology beyond glycemic control alone. However, further long-term studies are needed to clarify their effects on remodeling reversal, arrhythmia burden, and cardiovascular mortality.
01Findings
What the study reported
- Drugs
- Semaglutide, Tirzepatide
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Cvd status
- cardiovascular disease present in population (see abstract)
- Baseline condition
- heart failure with preserved ejection fraction
Study quality details
- Study design
- Systematic review
- Sample size
- not extracted
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Heart failure with preserved ejection fraction (HFpEF) remains a clinically heterogeneous syndrome with limited disease-modifying therapeutic options, particularly among patients with obesity-related cardiometabolic dysfunction. Increasing evidence suggests that obesity-associated HFpEF represents a distinct inflammatory and metabolically active phenotype characterized by visceral adiposity, endothelial dysfunction, congestion physiology, impaired exercise capacity, and adverse cardiac remodeling. Incretin-based therapies, including glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists, have recently emerged as promising interventions within this evolving therapeutic landscape. This systematic review evaluated contemporary randomized clinical evidence examining the effects of semaglutide and tirzepatide in obesity-related HFpEF. A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science for studies published between January 2020 and July 2025. Nine studies met the predefined eligibility criteria, including landmark randomized controlled trials, pooled analyses, and mechanistic imaging and biomarker substudies. Across the included studies, incretin-based therapies consistently improved heart failure-related symptoms, exercise capacity, quality of life, inflammatory biomarkers, and body weight, while also demonstrating favorable effects on structural remodeling, congestion-related physiology, and cardiovascular-kidney interactions. Mechanistic analyses suggested potential benefits involving reductions in left ventricular mass, paracardiac adipose tissue, inflammatory burden, plasma volume expansion, and markers of myocardial and renal injury. Collectively, the current evidence supports the growing role of incretin-based therapies as promising phenotype-oriented interventions in obesity-related HFpEF and raises the possibility that targeted cardiometabolic modulation may influence multiple domains of disease pathophysiology beyond glycemic control alone. However, further long-term studies are needed to clarify their effects on remodeling reversal, arrhythmia burden, and cardiovascular mortality.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42382865 first ingestion |