Evidence map›Paper›PMID 40305708›Full record

Trial reportThe New England journal of medicine2025

Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.

Arun J Sanyal, Philip N Newsome, Iris Kliers, Laura Harms Østergaard, Michelle T Long, Mette Skalshøi Kjær, Anna M G Cali, Elisabetta Bugianesi, Mary E Rinella, Michael Roden and 2 more

2 registry-linked trialsAbstract readRandomized Controlled TrialClinical Trial, Phase IIIMulticenter Study
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 580 papers, 13 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
580citing papers in PubMed, 13 pooled it
–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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT04822181 phase3active not recruitingnot on this map

The Effect of Semaglutide in Subjects With Non-cirrhotic Non-alcoholic Steatohepatitis

TypeinterventionalSponsorNovo Nordisk A/SRan2021 to 2029Enrolled1,205ConditionsNon-alcoholic SteatohepatitisArmsSemaglutide, Placebo
NCT07566299 completednot on this map

Early GLP-1 Receptor Agonist and SGLT2 Inhibitor Add-On Strategies in Adults With Obesity, Type 2 Diabetes, Cardiovascular-Kidney-Metabolic Syndrome Stage 2-3, and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Target Trial Emulation

TypeobservationalSponsorChung Shan Medical UniversityRan2017 to 2026Enrolled118,805ConditionsObesity Type 2 Diabetes Mellitus, Cardiovascular-kidney-metabolic Syndrome, Metabolic Dysfunction-Associated Steatotic Liver Disease
3 · Its place in the literature

Who cites it

580 citing papers in PubMed, 13 syntheses or guidelines pooled it.

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  12. [Construction norms for the tiered diagnosis and treatment and standardized management center of metabolic-associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026
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520 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Arun J SanyalStravitz-Sanyal Institute for Liver Disease and Metabolic Health, Virginia Commonwealth University School of Medicine, Richmond.
Philip N NewsomeRoger Williams Institute of Liver Studies, Faculty of Life Sciences and Medicine, King's College London, Foundation for Liver Research and King's College Hospital, London.
Iris KliersNovo Nordisk, Bagsværd, Denmark.
Laura Harms ØstergaardNovo Nordisk, Bagsværd, Denmark.
Michelle T LongNovo Nordisk, Bagsværd, Denmark.
Mette Skalshøi KjærNovo Nordisk, Bagsværd, Denmark.ORCID 0000-0001-6322-4077
Anna M G CaliNovo Nordisk, Bagsværd, Denmark.
Elisabetta BugianesiDepartment of Medical Sciences, University of Turin, Turin, Italy.
Mary E RinellaDivision of Gastroenterology, Hepatology, and Nutrition, University of Chicago, Chicago.
Michael RodenDepartment of Endocrinology and Diabetology, Faculty of Medicine, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Vlad RatziuSorbonne Université, Institute for Cardiometabolism and Nutrition, Hôpital Pitié-Salpêtrière, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris.
ESSENCE Study Group

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundSemaglutide, a glucagon-like peptide-1 receptor agonist, is a candidate for the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

methodsIn this ongoing phase 3, multicenter, randomized, double-blind, placebo-controlled trial, we assigned 1197 patients with biopsy-defined MASH and fibrosis stage 2 or 3 in a 2:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo for 240 weeks. The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1). The primary end points for part 1 were the resolution of steatohepatitis without worsening of liver fibrosis and reduction in liver fibrosis without worsening of steatohepatitis.

resultsResolution of steatohepatitis without worsening of fibrosis occurred in 62.9% of the 534 patients in the semaglutide group and in 34.3% of the 266 patients in the placebo group (estimated difference, 28.7 percentage points; 95% confidence interval [CI], 21.1 to 36.2; P<0.001). A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% of those in the placebo group (estimated difference, 14.4 percentage points; 95% CI, 7.5 to 21.3; P<0.001). Results for the three secondary outcomes that were included in the plan to adjust for multiple testing were as follows: combined resolution of steatohepatitis and reduction in liver fibrosis was reported in 32.7% of the patients in the semaglutide group and in 16.1% of those in the placebo group (estimated difference, 16.5 percentage points; 95% CI, 10.2 to 22.8; P<0.001). The mean change in body weight was -10.5% with semaglutide and -2.0% with placebo (estimated difference, -8.5 percentage points; 95% CI, -9.6 to -7.4; P<0.001). Mean changes in bodily pain scores did not differ significantly between the two groups. Gastrointestinal adverse events were more common in the semaglutide group.

conclusionsIn patients with MASH and moderate or advanced liver fibrosis, once-weekly semaglutide at a dose of 2.4 mg improved liver histologic results. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT04822181.).

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsLiver CirrhosisNon-alcoholic Fatty Liver DiseaseAdultAgedBiopsyDouble-Blind MethodDrug Administration ScheduleFemaleFollow-Up StudiesGlucagon-Like Peptide 1HumansInjections, SubcutaneousLiverMaleMiddle AgedGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsSemaglutide

Identifiers

PMID40305708

What OpenQuestion holds

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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 OpenQuestion graph.