Evidence map›Paper›PMID 33185364›Full record

Trial reportThe New England journal of medicine2021

A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis.

Philip N Newsome, Kristine Buchholtz, Kenneth Cusi, Martin Linder, Takeshi Okanoue, Vlad Ratziu, Arun J Sanyal, Anne-Sophie Sejling, Stephen A Harrison, NN9931-4296 Investigators

4 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 1,001 papers, 17 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1,001citing papers in PubMed, 17 pooled it
118.8field-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.

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.

NCT06060392 narecruitingstarted 2023, after this paper: background citation

Effect of Oral Semaglutide on Liver Fat and Body Composition in Liver Transplant Recipients With Diabetes Mellitus: Sema-Lit

Ran2023Enrolled50Registered outcomes17Posted comparisons0ConditionsDiabete Mellitus, Liver Transplant; ComplicationsArmsSemaglutide Pill
PMID 35439567PMID 19938117PMID 22025886PMID 22431131PMID 22554256PMID 25482832other papers from this trial
Open the trial in the graph
NCT07466017 phase2active not recruitingstarted 2026, after this paper: background citation

A Randomized, Double-blind, Placebo-controlled, Parallel-group Phase II Study to Evaluate the Efficacy and Safety of CS060380 Tablets in Patients With Metabolic Dysfunction-associated Steatohepatitis (MASH) and Obesity.

Ran2026Enrolled130Registered outcomes3Posted comparisons0ConditionsMetabolic Dysfunction-associated Steatohepatitis (MASH), ObesityArmsCS060380, Placebo, semaglutide
Open the trial in the graph
NCT02970942 phase2completednot on this map

This Trial is Conducted Globally. The Aim of This Trial is to Investigate Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis

TypeinterventionalSponsorNovo Nordisk A/SRan2016 to 2020Enrolled320ConditionsHepatobiliary Disorders, Non-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

1,001 citing papers in PubMed, 17 syntheses or guidelines pooled it, 1,791 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 1 institution in 5 countries.

Philip N NewsomeFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Kristine BuchholtzFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Kenneth CusiFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Martin LinderFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Takeshi OkanoueFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Vlad RatziuFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Arun J SanyalFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Anne-Sophie SejlingFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Stephen A HarrisonFrom the National Institute for Health Research Biomedical Research Centre at University Hospitals Birmingham NHS Foundation Trust and the Centre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, and the Liver Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham (P.N.N.), and the Radcliffe Department of Medicine, University of Oxford, Oxford (S.A.H.) - all in the United Kingdom; Novo Nordisk, Søborg, Denmark (K.B., M.L., A.-S.S.); the Division of Endocrinology, Diabetes, and Metabolism, University of Florida, Gainesville (K.C.); the Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan (T.O.); the Institute of Cardiometabolism and Nutrition, Sorbonne Université, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, INSERM Unité Mixte de Recherche Scientifique 1138 Centre de Recherche des Cordeliers, Paris (V.R.); and the Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
NN9931-4296 Investigators
University Hospitals Birmingham NHS Foundation Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.

methodsWe conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.

resultsIn total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed.

conclusionsThis phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).

Indexed as

AdolescentAdultAgedAmylasesBiopsyDiabetes Mellitus, Type 2Dose-Response Relationship, DrugDouble-Blind MethodFemaleGlucagon-Like PeptidesHumansInjections, SubcutaneousLipaseLiverLiver CirrhosisMaleAmylasesGlucagon-Like PeptidesLipaseSemaglutide

Identifiers

PMID33185364
OpenAlexW3102426258

What OpenQuestion holds

Texttitle and abstract
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 OpenQuestion graph.