Evidence map›GLP-1 receptor agonists × cardiac & vascular function›PMID 38599221›Full record

Trial reportLancet (London, England)2024

Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials.

Javed Butler, Sanjiv J Shah, Mark C Petrie, Barry A Borlaug, Steen Z Abildstrøm, Melanie J Davies, G Kees Hovingh, Dalane W Kitzman, Daniél Vega Møller, Subodh Verma and 23 more

2 registry-linked trialsOpen access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Lancet (London, England), 2024. The graph read 1 number from its abstract, feeding 1 cell of the map: it supports the treatment in 1. It reports registered trial NCT04788511. Cited by 153 papers, 4 of them syntheses that pooled it.

1number the graph read from it
1cell of the map it votes in
153citing papers in PubMed, 4 pooled it
116.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

← favours the comparatorfavours the treatment →
9.800 · no effect
Cardiac & vascular functionfavours the treatment · against placebo · heart_failure, obesityfeeds one cell of the map
Δ 7.505.30 to 9.80p<0.0001
Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7.5 points [95% CI 5.3 to 9.8]; p<0.0001; mean between-group difference in bodyweight at week 52 -8.4% [-9.2 to -7.5]; p<0.0001).
FeedsGLP-1 receptor agonists×cardiac & vascular function

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GLP-1 receptor agonists×cardiac & vascular function

SupportsOpen on the map →What to test next →

6 readable studies in this cell: 3 favour the treatment, 2 find no difference, 1 favour the comparator.

Belief with this paper
0.50contested · 3 families support, 1 contradict · against placebo
Without it
0.50This paper does not move the number.
← favours the comparatorfavours the treatment →
0 · no effect
This paper529 enrolled · 2021
Δ 7.505.30 to 9.80
Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 …PMID 38587233 · 617 enrolled · 2021
change 0.670.55 to 0.80
NCT0488111060 enrolled · 2021
Δ 25.121.8 to 28.3
Effect of liraglutide on cardiac function in patients with type 2 diab…PMID 31039778 · 50 enrolled · 2013
Δ 1.00
Semaglutide and NT-proBNP in Obesity-Related HFpEF: Insights From the …PMID 38819334 · 2024
Δ 4.500.80 to 8.20
Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ven…PMID 27790809 · 2017
Δ -0.80-2.10 to 0.50
4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04788511 phase3completed

Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction

Ran2021Enrolled529Registered outcomes15Posted comparisons2ConditionsObesityArmsPlacebo (semaglutide), semaglutide
PMID 37622681PMID 37635157other papers from this trial
Open the trial in the graph
NCT04916470 phase3completed

Effect of Semaglutide 2.4 mg Once-weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction, and Type 2 Diabetes

Ran2021Enrolled617Registered outcomes23Posted comparisons0ConditionsHeart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2ArmsPlacebo (semaglutide), semaglutide
PMID 37294245other papers from this trial
Open the trial in the graph
5 · Its place in the literature

Who cites it

153 citing papers in PubMed, 4 syntheses or guidelines pooled it, 290 citations in OpenAlex.

  1. Pooled it
  2. Cardiovascular Safety Profile of Semaglutide and Variations by Sex, Race, and Kidney Function: A Systematic Review and Meta-analysis.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2025 · on this map
    Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
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  13. Impact of semaglutide on health outcomes and mood in obese heart failure patients: a retrospective analysis.Clinical research in cardiology : official journal of the German Cardiac Society · 2026
    Article
  14. Metabolic-inflammatory burden predicts mortality in heart failure across population and ICU cohorts.International journal of cardiology. Cardiovascular risk and prevention · 2026
    Article
  15. Review
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  17. Review
  18. Article
  19. Article
  20. Review

93 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

33 authors at 20 institutions in 17 countries.

Javed ButlerBaylor Scott & White Research Institute, Dallas, TX, USA; Department of Medicine, University of Mississippi, Jackson, MS, USA.
Sanjiv J ShahDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Mark C PetrieSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK.
Barry A BorlaugDepartment of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Steen Z AbildstrømNovo Nordisk, Søborg, Denmark.
Melanie J DaviesDiabetes Research Centre, University of Leicester, Leicester, UK; National Institute for Health and Care Research Leicester Biomedical Research Centre, Leicester, UK.
G Kees HovinghNovo Nordisk, Søborg, Denmark.
Dalane W KitzmanDepartment of Cardiovascular Medicine and Section on Geriatrics and Gerontology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Daniél Vega MøllerNovo Nordisk, Søborg, Denmark.
Subodh VermaDivision of Cardiac Surgery, Li Ka Shing Knowledge Institute of St Michael's Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
Mette Nygaard EinfeldtNovo Nordisk, Søborg, Denmark.
Marie L LindegaardNovo Nordisk, Søborg, Denmark.
Søren RasmussenNovo Nordisk, Søborg, Denmark.
Walter AbhayaratnaCollege of Health and Medicine, Australian National University, Canberra, ACT, Australia.
Fozia Z AhmedDivision of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
Tuvia Ben-GalHeart Failure Unit, Department of Cardiology, Rabin Medical Center, Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Vijay ChopraMax Super Speciality Hospital, Saket, New Delhi, India.
Justin A EzekowitzCanadian VIGOUR Centre, University of Alberta, Edmonton, AB, Canada.
Michael FuSection of Cardiology, Department of Medicine, Sahlgrenska University Hospital-Ostra, Gothenburg, Sweden.
Hiroshi ItoDepartment of General Internal Medicine 3, Kawasaki Medical School, Okayama, Japan.
Małgorzata LelonekDepartment of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland.
Vojtěch MelenovskýInstitute for Clinical and Experimental Medicine-IKEM, Prague, Czech Republic.
Bela MerkelyHeart and Vascular Centre, Semmelweis University, Budapest, Hungary.
Julio NúñezHospital Clínico Universitario de Valencia, INCLIVA, Universidad de Valencia, Valencia, Spain; Centro de Investigación Biomédica en Red Cardiovascular, Valencia, Spain.
Eduardo PernaInstituto de Cardiologia J F Cabral, Corrientes, Argentina.
Morten SchouDepartment of Cardiology, Herlev-Gentofte Hospital, Hellerup, Denmark; Department of Clinical Medicine, University of Copenhagen, Herlev, Denmark.
Michele SenniAzienda Socio Sanitaria Territorial Papa Giovanni XXIII, Bergamo, Italy.
Kavita SharmaHeart Failure & Cardiac Transplantation, Johns Hopkins University Heart Failure with Preserved Ejection Fraction Program, Johns Hopkins Hospital, Baltimore, MD, USA.
Peter van der MeerDepartment of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Dirk Von LewinskiMedical University of Graz, Graz, Austria.
Dennis WolfCardiology and Angiology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Mikhail N KosiborodDepartment of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, Kansas City, MO, USA; University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. Electronic address: mkosiborod@saint-lukes.org.
STEP-HFpEF Trial Committees and Investigators
Novo Nordisk (Denmark) · DKAustralian National University · AUBaylor Scott & White Health · USCanadian VIGOUR Centre · CACentro de Investigación Biomédica en Red · ESInstitute of Clinical and Experimental Medicine · CZJohns Hopkins University · USKawasaki Medical School · JPMax Super Speciality Hospital · INMayo Clinic in Arizona · USMedical University of Graz · ATMedical University of Lodz · PLNorthwestern University · USOspedale Papa Giovanni XXIII · ITRabin Medical Center · ILSahlgrenska University Hospital · SESemmelweis University · HUSt. Michael's Hospital · CAUniversity of Copenhagen · DKUniversity of Freiburg · DE

Funding

Wake Forest Claude D. Pepper OAIC - RenewalP30AG021332 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2002 to 2025
$7.7M
Physical Rehabilitation for Older Patients with Acute HFpEF-The REHAB-HFpEF TrialR01AG078153 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$6.8M
HeartShare DeCODE-HF: Data translation center to Combine Omics, Deep phenotyping, and Electronic health records for Heart Failure subtypes and treatment targetsU54HL160273 · NORTHWESTERN UNIVERSITY · 2025 to 2025
$3.3M
Pepper OAIC Coordinating CenterU24AG059624 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$640k
Wake Forest Atrium HeartShare Clinical CenterU01HL160272 · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$529k
NHLBI NIH HHS R01 HL107577NHLBI NIH HHS R01 HL127028NHLBI NIH HHS R01 HL140731NHLBI NIH HHS R01 HL149423NHLBI NIH HHS U01 HL160272NHLBI NIH HHS U54 HL160273NIA NIH HHS P30 AG021332NIA NIH HHS R01 AG078153NIA NIH HHS U01 AG076928NIA NIH HHS U24 AG059624
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundIn the STEP-HFpEF (NCT04788511) and STEP-HFpEF DM (NCT04916470) trials, the GLP-1 receptor agonist semaglutide improved symptoms, physical limitations, bodyweight, and exercise function in people with obesity-related heart failure with preserved ejection fraction. In this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, we aimed to provide a more definitive assessment of the effects of semaglutide across a range of outcomes and to test whether these effects were consistent across key patient subgroups.

methodsWe conducted a prespecified pooled analysis of individual patient data from STEP-HFpEF and STEP-HFpEF DM, randomised, double-blind, placebo-controlled trials at 129 clinical research sites in 18 countries. In both trials, eligible participants were aged 18 years or older, had heart failure with a left ventricular ejection fraction of at least 45%, a BMI of at least 30 kg/m

findingsBetween March 19, 2021 and March 9, 2022, 529 people were randomly assigned in STEP-HFpEF, and between June 27, 2021 and Sept 2, 2022, 616 were randomly assigned in STEP-HFpEF DM. Overall, 1145 were included in our pooled analysis, 573 in the semaglutide group and 572 in the placebo group. Improvements in KCCQ-CSS and reductions in bodyweight between baseline and week 52 were significantly greater in the semaglutide group than in the placebo group (mean between-group difference for the change from baseline to week 52 in KCCQ-CSS 7·5 points [95% CI 5·3 to 9·8]; p<0·0001; mean between-group difference in bodyweight at week 52 -8·4% [-9·2 to -7·5]; p<0·0001). For the confirmatory secondary endpoints, 6-min walk distance (mean between-group difference at week 52 17·1 metres [9·2 to 25·0]) and the hierarchical composite endpoint (win ratio 1·65 [1·42 to 1·91]) were significantly improved, and CRP concentrations (treatment ratio 0·64 [0·56 to 0·72]) were significantly reduced, in the semaglutide group compared with the placebo group (p<0·0001 for all comparisons). For the dual primary endpoints, the efficacy of semaglutide was largely consistent across multiple subgroups, including those defined by age, race, sex, BMI, systolic blood pressure, baseline CRP, and left ventricular ejection fraction. 161 serious adverse events were reported in the semaglutide group compared with 301 in the placebo group.

interpretationIn this prespecified pooled analysis of the STEP-HFpEF and STEP-HFpEF DM trials, semaglutide was superior to placebo in improving heart failure-related symptoms and physical limitations, and reducing bodyweight in participants with obesity-related heart failure with preserved ejection fraction. These effects were largely consistent across patient demographic and clinical characteristics. Semaglutide was well tolerated.

fundingNovo Nordisk.

Indexed as

Glucagon-Like PeptidesHeart FailureObesityStroke VolumeAgedDouble-Blind MethodFemaleHumansMaleMiddle AgedSemaglutideTreatment OutcomeGlucagon-Like PeptidesSemaglutide

Identifiers

PMID38599221
PMCPMC11317105
OpenAlexW4394061375

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.