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

Sanyal AJ, Newsome PN, Kliers I, Østergaard LH, Long MT, Kjær MS, Cali AMG, Bugianesi E, Rinella ME, Roden M, Ratziu V

The New England journal of medicine30 Apr 2025Cited by 778 (Europe PMC)

PMID40305708DOI10.1056/nejmoa2413258PepBankPUB-40305708

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study6

6 results from studies that gave the peptide. 6 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis stage 2 or 3, semaglutide 2.4 mg led to resolution of steatohepatitis without worsening of fibrosis in more patients than placebo at week 72.
In plain wordsIn adults with MASH and liver scarring, more patients on semaglutide than on placebo had their liver inflammation clear up.
Peptide
Semaglutide
Outcome
IncreaseResolution of steatohepatitis without worsening of fibrosis
Study
n = 800
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
2.4 mg once weekly · subcutaneous · 72 weeks (interim analysis; planned 240 weeks)As given in this study (human).
Measurements
Resolution of steatohepatitis
62.9%
semaglutide
Resolution of steatohepatitis
34.3%
placebo
Estimated difference
28.7 percentage points
semaglutide vs placebo
Source sentences
Summary
Resolution 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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1).
Report a problemFND-4030570801
02HumanRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis stage 2 or 3, semaglutide 2.4 mg led to a reduction in liver fibrosis without worsening of steatohepatitis in more patients than placebo at week 72.
In plain wordsIn adults with MASH and liver scarring, more patients on semaglutide than on placebo had less liver scarring.
Peptide
Semaglutide
Outcome
IncreaseReduction in liver fibrosis without worsening of steatohepatitis
Study
n = 800
Comparator
Placebo
Analysis
Primary
Outcome group
Liver fat and liver function · Liver
Studied dose
2.4 mg once weekly · subcutaneous · 72 weeks (interim analysis; planned 240 weeks)As given in this study (human).
Measurements
Fibrosis reduction
36.8%
semaglutide
Fibrosis reduction
22.4%
placebo
Estimated difference
14.4 percentage points
semaglutide vs placebo
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1).
Report a problemFND-4030570802
03HumanRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis stage 2 or 3, semaglutide 2.4 mg led to combined resolution of steatohepatitis and reduction in fibrosis in more patients than placebo.
In plain wordsIn adults with MASH and liver scarring, more patients on semaglutide than on placebo had both less liver inflammation and less scarring.
Peptide
Semaglutide
Outcome
IncreaseCombined resolution of steatohepatitis and reduction in liver fibrosis
Study
n = 800
Comparator
Placebo
Analysis
Secondary
Outcome group
Liver fat and liver function · Liver
Studied dose
2.4 mg once weekly · subcutaneous · 72 weeks (interim analysis; planned 240 weeks)As given in this study (human).
Measurements
Combined resolution and fibrosis reduction
32.7%
semaglutide
Combined resolution and fibrosis reduction
16.1%
placebo
Estimated difference
16.5 percentage points
semaglutide vs placebo
Source sentences
Summary
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 (es…
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1).
Report a problemFND-4030570803
04HumanRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis stage 2 or 3, semaglutide 2.4 mg reduced body weight more than placebo.
In plain wordsIn adults with MASH and liver scarring, body weight fell more on semaglutide than on placebo.
Peptide
Semaglutide
Outcome
DecreaseMean change in body weight
Study
n = 800
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
2.4 mg once weekly · subcutaneous · 72 weeks (interim analysis; planned 240 weeks)As given in this study (human).
Measurements
Mean body weight change
−10.5%
semaglutide
Mean body weight change
−2%
placebo
Estimated difference
−8.5 percentage points
semaglutide vs placebo
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1).
Report a problemFND-4030570804
05HumanRandomized controlled trialEfficacy outcome
In adults with MASH and fibrosis stage 2 or 3, bodily pain score changes did not differ significantly between semaglutide 2.4 mg and placebo.
In plain wordsIn adults with MASH and liver scarring, pain scores changed about the same on semaglutide and on placebo.
Peptide
Semaglutide
Outcome
No significant changeMean change in bodily pain scores
Study
n = 800
Comparator
Placebo
Analysis
Secondary
Outcome group
Pain · Nervous system and cognition
Studied dose
2.4 mg once weekly · subcutaneous · 72 weeks (interim analysis; planned 240 weeks)As given in this study (human).
Source sentences
Summary
Mean changes in bodily pain scores did not differ significantly between the two groups.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1).
Report a problemFND-4030570805
06HumanRandomized controlled trialSafety outcome
In adults with MASH and fibrosis stage 2 or 3, gastrointestinal adverse events were more common with semaglutide 2.4 mg than with placebo.
In plain wordsIn adults with MASH and liver scarring, stomach and gut side effects were more common on semaglutide than on placebo.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal adverse events
Study
n = 800
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
2.4 mg once weekly · subcutaneous · 72 weeks (interim analysis; planned 240 weeks)As given in this study (human).
Source sentences
Summary
Gastrointestinal adverse events were more common in the semaglutide group.
2 context sentences(design, population, supporting numbers)
Summary · context
In 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.
Summary · context
The results of a planned interim analysis conducted at week 72 involving the first 800 patients are reported here (part 1).
Report a problemFND-4030570806

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

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 ongoing · source ClinicalTrials.gov (opens in a new tab)

Active, not recruitingPhase 3NCT04822181

Research Study on Whether Semaglutide Works in People With Non-alcoholic Steatohepatitis (NASH)

Novo Nordisk A/Sn = 1,2051 Apr 2021 to est. 25 Apr 2029

Non-alcoholic Steatohepatitis

Trial page ClinicalTrials.govUpdated 13 Oct 2026

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.

Version 2Current
9 Oct 2026, 18:17 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

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