Trial reportNature medicine2026

Semaglutide on liver fibrosis and heart outcomes in patients at high risk of liver fibrosis: a prespecified analysis of the SELECT randomized trial.

Sebastian M Meyhöfer, Bertrand Cariou, Cintia Cercato, Helen M Colhoun, John Deanfield, Michelle T Long, Ole Kleist Jeppesen, A Michael Lincoff, Ildiko Lingvay, Jorge Plutzky and 7 more

2 registry-linked trialsAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Nature medicine, 2026. The graph read 1 number from its abstract, feeding 1 cell of the map: it supports the treatment in 1. It reports registered trial NCT03574597. Cited by 1 paper.

1number the graph read from it
1cell of the map it votes in
1citing papers in PubMed
field-weighted citation impact
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 treatmentfavours the comparator →
1 · no effect
Liver & MASLDfavours the treatment · against placebo · ascvd, liverfeeds one cell of the map
HR 0.720.71 to 0.73P < 0.0001
Semaglutide led to a 28% greater decrease in fatty liver index versus placebo (HR 0.72; 95% CI 0.71-0.73; P < 0.0001).

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×liver & masld

SupportsOpen on the map →What to test next →

4 readable studies in this cell: 0 favour the treatment, 3 find no difference, 1 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 contradict · against placebo
Without it
0.25This paper moves it by +0.25. It would be no deciding trial.
← favours the comparatorfavours the treatment →
0 · no effect
NCT04019197108 enrolled · 2019
β coefficient 3.55-0.30 to 7.41
NCT0355599451 enrolled · 2018
Δ -22.0-34.5 to -9.43
estimated mean treatment effect 0.03-0.09 to 0.04

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

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.

NCT03574597 phase3completed

SELECT - Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity

Ran2018Enrolled17,604Registered outcomes29Posted comparisons1ConditionsObesity, OverweightArmsPlacebo (semaglutide), semaglutide
PMID 33567185PMID 37952131PMID 32916609other papers from this trial
Open the trial in the graph
NCT07567378 not yet recruiting

Cartilage, Arthropathy and Imaging Under Tirzepatide in Zone-stratified Cohorts (CARTIZ): A Prospective Observational Multi-Institutional Registry of the VAT-Articular-Cardiac-Aging Axis in Adults Exposed to Tirzepatide in Mexico, With Quantitative Knee Cartilage T2 Mapping, Cardiac CT Epicardial Adipose Tissue Radiomic Phenotyping, HLA Stratification, Longitudinal Multi-Frequency Bioimpedance Body Composition, and a Prespecified Surgical Tissue Acquisition Subcohort

Ran2026Enrolled30Registered outcomes14Posted comparisons0ConditionsAtrial Fibrillation (AF), Coronary Artery Disease, Diabetes (DM), Heart FailureArmsTirzepatide
Open the trial in the graph
5 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

17 authors.

Sebastian M MeyhöferClinical, Medical & Regulatory, Novo Nordisk Pharma GmbH, Mainz, Germany. SMYF@novonordisk.com.ORCID http://orcid.org/0000-0003-2034-5922
Bertrand CariouNantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.ORCID http://orcid.org/0000-0002-1580-8040
Cintia CercatoObesity Unit, Department of Endocrinology, Clinical Hospital of the University of São Paulo, São Paulo, Brazil.
Helen M ColhounInstitute of Genetics and Cancer, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-8345-3288
John DeanfieldInstitute of Cardiovascular Science, University College London, London, UK.
Michelle T LongNovo Nordisk A/S, Søborg, Denmark.ORCID http://orcid.org/0000-0001-6131-3981
Ole Kleist JeppesenNovo Nordisk A/S, Søborg, Denmark.
A Michael LincoffDepartment of Cardiovascular Medicine, Cleveland Clinic and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH, USA.
Ildiko LingvayDepartment of Internal Medicine/Endocrinology and Peter O'Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0001-7006-7401
Jorge PlutzkyCardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7194-9876
Philip N NewsomeRoger Williams Institute of Liver Studies, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London, UK.
Stephen J NichollsVictorian Heart Institute, Monash University, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0002-9668-4368
Maria QuirogaNovo Nordisk A/S, Søborg, Denmark.
Ferruccio SantiniObesity and Lipodystrophy Centre, University Hospital of Pisa, Pisa, Italy.ORCID http://orcid.org/0000-0002-1706-0822
Arun J SanyalDivision of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.ORCID http://orcid.org/0000-0001-8682-5748
Steven E KahnDepartment of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
SELECT Trial Investigators

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

In the SELECT trial, once-weekly subcutaneous semaglutide reduced major adverse cardiovascular events (MACE) by 20% versus placebo in patients with atherosclerotic cardiovascular disease and obesity but without diabetes. We examined semaglutide in SELECT patients at high risk for substantial liver fibrosis in a prespecified secondary analysis. Liver biochemical tests and steatosis risk according to fatty liver index were assessed over 104 weeks. Subgroup analyses of the primary MACE (a composite endpoint including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) outcome used baseline Fibrosis-4 scores ≥ 1.3, age-specific (≥1.3 (<65 years) or ≥2.0 (≥65 years)) and any age with Fibrosis-4 > 2.67. MACE was reduced by 26% (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63-0.88; P = 0.0004), 21% (HR 0.79; 95% CI 0.63-0.98; P = 0.035) and 34% (HR 0.66; 95% CI 0.39-1.10; P = 0.11), respectively. Semaglutide led to a 28% greater decrease in fatty liver index versus placebo (HR 0.72; 95% CI 0.71-0.73; P < 0.0001). In conclusion, semaglutide reduced MACE versus placebo in patients at risk for substantial liver fibrosis, as seen in the overall SELECT population. ClinicalTrials.gov registration no. NCT03574597.

Indexed as

Cardiovascular DiseasesGlucagon-Like PeptidesLiver CirrhosisObesityAgedFatty LiverFemaleHumansMaleMiddle AgedRisk FactorsSemaglutideGlucagon-Like PeptidesSemaglutide

Identifiers

PMID41928037
PMCPMC13190271

What Socratic holds

Texttitle and abstract
LicenceCC BY
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.