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Study · Systematic review · n = 4,216 · 2026

3 results

Semaglutide for the Silent Phenotype: A Translational Signal in Obesity-Driven HFpEF.

Ceravolo R, Lucà F, Gulizia MM, Nardi F, Grimaldi M, Gelsomino S

The American journal of cardiology24 Jun 2026

PMID42342009 (opens in a new tab)DOI10.1016/j.amjcard.2026.06.015 (opens in a new tab)PepBankPUB-42342009
Publisher pagePubMedAsk about this study
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Summary

Obesity-related heart failure with preserved ejection fraction (HFpEF) represents an increasingly prevalent clinical phenotype characterized by exercise intolerance, systemic inflammation, and limited therapeutic options. Semaglutide, a glucagon-like peptide-1 receptor agonist approved for obesity management, has shown favorable effects on symptoms and cardiometabolic markers in patients with HFpEF and obesity, but the overall clinical profile of semaglutide across randomized trials and its relevance within the broader HFpEF therapeutic landscape remain incompletely defined. We conducted a systematic review and meta-analysis of randomized controlled trials evaluating semaglutide versus placebo in adults with HFpEF and obesity. MEDLINE, Embase, and CENTRAL were searched through February 2025. Six randomized trials (n = 4,216 participants) met inclusion criteria. Primary outcomes included changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP), Kansas City Cardiomyopathy Questionnaire (KCCQ) score, and heart-failure hospitalization. Random-effects models were used for pooled analyses. Semaglutide significantly reduced NT-proBNP levels (mean difference -119.7 pg/ml; 95% CI -144.4 to -95.1; p <0.001) and improved KCCQ scores in trials enrolling HFpEF populations (mean difference +8.27 points; 95% CI 6.04 to 10.50; p <0.001). Semaglutide was also associated with a lower risk of heart-failure hospitalization (odds ratio 0.81; 95% CI 0.75 to 0.88; p <0.001). Between-study heterogeneity was low for primary outcomes, and sensitivity analyses confirmed the robustness of the pooled estimates, while meta-regression analyses did not identify significant modification of treatment effects by baseline C-reactive protein levels. In conclusion, semaglutide therapy in obesity-related HFpEF was associated with improvements in biomarkers, symptoms, and heart-failure hospitalization across randomized trials, providing a quantitative synthesis of emerging evidence supporting metabolic-targeted strategies in this increasingly recognized HFpEF phenotype.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

3 results from studies that gave the peptide. 3 results from people.

  1. 01HumanSystematic reviewEfficacy outcome

    In adults with HFpEF and obesity, semaglutide significantly reduced NT-proBNP versus placebo in a meta-analysis of randomized trials.

    In plain wordsIn adults with obesity and a type of heart failure, trials pooled together showed semaglutide lowered a heart-strain blood marker more than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseNT-proBNP mean difference
    Study

    n = 4,216

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    NT-proBNP mean difference
    −119.7 pg/ml
    semaglutide vs placebo

    Source sentences

    Summary
    Semaglutide significantly reduced NT-proBNP levels (mean difference -119.7 pg/ml; 95% CI -144.4 to -95.1; p <0.001)
    2 context sentences
    Summary · context
    We conducted a systematic review and meta-analysis of randomized controlled trials evaluating semaglutide versus placebo in adults with HFpEF and obesity.
    Summary · context
    Six randomized trials (n = 4,216 participants) met inclusion criteria.
  2. 02HumanSystematic reviewEfficacy outcome

    In adults with HFpEF and obesity, semaglutide improved KCCQ scores versus placebo in a meta-analysis of randomized trials.

    In plain wordsIn adults with obesity and a type of heart failure, trials pooled together showed semaglutide improved symptom scores more than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseKCCQ score mean difference
    Study

    n = 4,216

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Heart function · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    KCCQ mean difference
    8.27 points
    semaglutide vs placebo

    Source sentences

    Summary
    improved KCCQ scores in trials enrolling HFpEF populations (mean difference +8.27 points; 95% CI 6.04 to 10.50; p <0.001).
    2 context sentences
    Summary · context
    We conducted a systematic review and meta-analysis of randomized controlled trials evaluating semaglutide versus placebo in adults with HFpEF and obesity.
    Summary · context
    Six randomized trials (n = 4,216 participants) met inclusion criteria.
  3. 03HumanSystematic reviewEfficacy outcome

    In adults with HFpEF and obesity, semaglutide was associated with a lower risk of heart-failure hospitalization versus placebo in a meta-analysis.

    In plain wordsIn adults with obesity and a type of heart failure, trials pooled together linked semaglutide to fewer hospital stays for heart failure than placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseHeart-failure hospitalization
    Study

    n = 4,216

    Comparator
    Placebo
    Analysis
    Primary
    Outcome group
    Cardiovascular events · Cardiovascular
    Studied dose
    Dose not stated

    Measurements

    Odds ratio
    0.81
    heart-failure hospitalization

    Source sentences

    Summary
    Semaglutide was also associated with a lower risk of heart-failure hospitalization (odds ratio 0.81; 95% CI 0.75 to 0.88; p <0.001).
    2 context sentences
    Summary · context
    We conducted a systematic review and meta-analysis of randomized controlled trials evaluating semaglutide versus placebo in adults with HFpEF and obesity.
    Summary · context
    Six randomized trials (n = 4,216 participants) met inclusion criteria.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    11 Oct 2026, 00:04 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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