Effect of Semaglutide Versus Placebo on Heart Failure With Preserved Ejection Fraction in Obese Patients: A Systematic Review
- Design
- Systematic review · 1463 participants · 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 2Systematic review (no pooled meta-analysis) of two RCTs and one retrospective cohort; the authors caution that few studies were included.
- Assessment
- Version 4 · Checked against the source by AI · Oct 19, 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.
Systematic review of three studies (two RCTs, one retrospective cohort; 1,463 people with obesity and HFpEF): over 52 weeks semaglutide lowered CRP and NT-proBNP (blood markers), body weight and symptoms compared with placebo. No cardiovascular event outcomes were reported, and the authors caution that few studies were included.
What the study reported
- Drugs
- Semaglutide
- Dose
- 2.4 mg once weekly
- Comparator
- placebo
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Not extracted
Who was studied
- Mean age
- about 69-70 years across the included studies
- Obesity status
- obesity/overweight present (all or most)
- Diabetes status
- mixed (one included RCT enrolled people with HFpEF and type 2 diabetes)
- Cvd status
- cardiovascular disease present in population (see abstract)
- Baseline condition
- heart failure with preserved ejection fraction
- Sample size
- 1463
Study quality details
- Study design
- Systematic review
- Sample size
- 1463
- Randomization
- n/a
- Blinding
- not stated
- Comparator
- placebo
- 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)
- Peer review status
- yes
How far the review's own results can be trusted
This record is a systematic review, so it is appraised with AMSTAR 2, which rates how far the review's own pooled results can be trusted. It does not grade the trials inside the review; those are appraised one by one.
On this scale High is the best rating. The levels run High, Moderate, Low, Critically low: Critically low confidence in the review is the worst rating a review can receive, and means it should not be relied on for an accurate summary. That is the opposite direction to the risk-of-bias scale used for single trials, where High is the worst.
Critically low confidence in the review · AMSTAR 2 · AI: two passes agreed (item splits settled by owner ruling)
Why: 3 critical items fail: review methods set out in a protocol before the review began; comprehensive literature search; list of excluded studies, with reasons.
What it is used for here: Used only to find trials. A review at this level does not supply a pooled result to any outcome in this collection; the trials it lists are appraised on their own.
| Item | Answer |
|---|---|
| 1 Research question and inclusion criteria include the PICO components | Yes |
| 2 · critical Review methods set out in a protocol before the review began | No — a critical flaw |
| 3 Choice of included study designs explained | No |
| 4 · critical Comprehensive literature search | No — a critical flaw |
| 5 Study selection done by two reviewers independently | Yes |
| 6 Data extraction done by two reviewers independently | No |
| 7 · critical List of excluded studies, with reasons | No — a critical flaw |
| 8 Included studies described in adequate detail | Partial Yes |
| 9 · critical Satisfactory technique for assessing risk of bias in the included studies | Partial Yes |
| 10 Funding of the included studies reported | No |
| 11 · critical Appropriate methods for combining results | Not applicable |
| 12 Effect of risk of bias on the pooled results assessed | Not applicable |
| 13 · critical Risk of bias taken into account when interpreting the results | Yes |
| 14 Differences between study results explained and discussed | No |
| 15 · critical Publication bias investigated and its likely impact discussed | Not applicable |
| 16 Review authors' conflicts of interest and funding reported | Yes |
Where the two reviewers differed: item 4 (comprehensive literature search): one read Partial Yes, the other No; settled at No by a recorded ruling; item 9 (satisfactory technique for assessing risk of bias in the included studies): one read No information, the other Partial Yes; settled at Partial Yes by a recorded ruling.
Two reviewers assessed the review independently against a written guide (AMSTAR 2 guide, version 1.1), from the full text and retrieved supplements, 2026-10-05.
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.
The source, as retrieved
Abstract
Heart failure (HF) is a major global health concern and can be classified into different phenotypes based on left ventricular ejection fraction (LVEF), including heart failure with preserved ejection fraction (HFpEF), reduced ejection fraction, and mildly reduced ejection fraction. This systematic review aims to determine the effect of semaglutide compared to placebo in obese patients with HFpEF. Following PRISMA 2020 guidelines, relevant studies published from January 2021 to August 2024 were identified through searches in PubMed and Science Direct. Randomized clinical trials (RCTs), cohort studies, and case-control studies were considered; however, only two randomized controlled trials (RCTs) and one retrospective cohort ultimately met the inclusion criteria, encompassing a total of 1463 participants with HFpEF and obesity. The risk of bias was evaluated utilizing the Cochrane risk of bias tool for RCTs and the Newcastle-Ottawa Scale (NOS) for the retrospective cohort. In each study, participants were divided into two groups receiving either semaglutide or placebo. The findings after a 52-week follow-up showed that treatment with semaglutide 2.4 mg once weekly resulted in a significant reduction in biomarkers associated with HF. Specifically, baseline C-reactive protein (CRP) values decreased by 43% and 42% in the RCTs and 37% in the retrospective cohort. NT-proBNP levels declined by 20.90% and 23.20% in the RCTs and 15.80% in the cohort, compared to the placebo group. The reductions in CRP and NT-proBNP are clinically relevant, as elevated levels of these biomarkers are associated with worse outcomes in HFpEF. In addition, participants in the semaglutide group experienced a reduction in body weight ranging from 9% to 13% across the three studies, while those in the placebo group showed weight loss between 2% and 7% across the studies. Functional improvement was also observed, with the Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) increasing by 13 to 16 points in the semaglutide group compared to the placebo. These results suggest that semaglutide may be a promising treatment for HFpEF in obese patients, offering not only significant weight loss but also improvements in biomarkers and quality of life. Therefore, semaglutide appears to provide potential cardiovascular and metabolic benefits in addition to its established weight-reducing effects, although findings should be interpreted with caution given the limited number of included studies.