Glucagon-Like Peptide-1 Receptor Agonists Improve MASH and Liver Fibrosis: A Meta-Analysis of Randomised Controlled Trials.

Mantovani A, Morandin R, Fiorio V, Lando MG, Stefan N, Tilg H, Byrne CD, Targher G

Liver international : official journal of the International Association for the Study of the Liver1 Sept 2025Cited by 22 (Europe PMC)

PMID40736113PMCIDPMC12309150DOI10.1111/liv.70256PepBankPUB-40736113

Download PDF PubMedAsk about this study

Jump to 5 results

Summary

Background/aimsThere is uncertainty regarding the hepatic efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH). We performed a meta-analysis of randomised controlled trials (RCTs) to examine the efficacy of GLP-1RAs in treating MASLD or MASH.MethodsWe systematically searched three electronic databases from inception until April 2025 to identify RCTs examining the efficacy of GLP-1RAs for the treatment of MASLD or MASH. The outcome measures included MASH resolution without worsening of fibrosis or improvement in at least one stage of fibrosis without worsening of MASH, along with reductions in liver fat content measured using magnetic resonance-based techniques. Meta-analysis was conducted using random-effects models.ResultsWe identified 13 phase 2 or phase 3 RCTs (1811 participants). These trials diagnosed MASLD or MASH through liver biopsy (n = 4) or magnetic resonance-based techniques (n = 9). Regardless of diabetes status, among individuals with MASH and moderate-to-advanced fibrosis, GLP-1RAs (especially semaglutide 2.4 mg/week) for up to 72 weeks were superior to placebo in achieving MASH resolution (n = 3 RCTs; pooled random-effects odds ratio 3.48, 95% CI 2.69-4.51; I² = 0%), and in improving liver fibrosis (pooled odds ratio 1.79, 95% CI 1.37-2.35; I² = 0%). Among individuals with MASH-related compensated cirrhosis (n = 1 RCT available only), semaglutide did not lead to MASH resolution or improved fibrosis compared to placebo. Furthermore, GLP-1RAs reduced magnetic resonance-measured liver fat content (n = 9; pooled mean difference: -4.50%, 95% CI -6.60 to -2.40%; I² = 95.9%).ConclusionsGLP-1RAs are a promising treatment option for MASLD or MASH. Further research is needed to evaluate the long-term effects of GLP-1RAs on liver-related clinical events.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

2 results from studies that gave the peptide. 2 results from people.

01HumanSystematic reviewEfficacy outcome
In adults with MASH-related compensated cirrhosis, semaglutide did not lead to MASH resolution compared with placebo (one RCT).
In plain wordsIn adults with MASH-related cirrhosis, semaglutide did not lead to MASH resolution compared with placebo in the one trial available.
Peptide
Semaglutide
Outcome
No significant changeMASH resolution in compensated cirrhosis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Among individuals with MASH-related compensated cirrhosis (n = 1 RCT available only), semaglutide did not lead to MASH resolution or improved fibrosis compared to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
We identified 13 phase 2 or phase 3 RCTs (1811 participants).
Show in the study text Report a problemFND-4073611303
02HumanSystematic reviewEfficacy outcome
In adults with MASH-related compensated cirrhosis, semaglutide did not improve fibrosis compared with placebo (one RCT).
In plain wordsIn adults with MASH-related cirrhosis, semaglutide did not improve fibrosis compared with placebo in the one trial available.
Peptide
Semaglutide
Outcome
No significant changeFibrosis improvement in compensated cirrhosis
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Studied dose
Dose not stated
Source sentences
Summary
Among individuals with MASH-related compensated cirrhosis (n = 1 RCT available only), semaglutide did not lead to MASH resolution or improved fibrosis compared to placebo.
1 context sentence(design, population, supporting numbers)
Summary · context
We identified 13 phase 2 or phase 3 RCTs (1811 participants).
Show in the study text Report a problemFND-4073611304

Studies that did not test the peptide alone3

In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Semaglutide.

03HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with MASH and moderate-to-advanced fibrosis, pooled GLP-1 receptor agonists (especially semaglutide 2.4 mg/week) were superior to placebo for MASH resolution.
In plain wordsIn adults with MASH and fibrosis, GLP-1 drugs as a group, mostly semaglutide, led to more MASH resolution than placebo.
Peptide
Semaglutide
Outcome
IncreaseMASH resolution (pooled GLP-1 receptor agonists)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Pooled odds ratio
3.48
MASH resolution
Source sentences
Summary
GLP-1RAs (especially semaglutide 2.4 mg/week) for up to 72 weeks were superior to placebo in achieving MASH resolution (n = 3 RCTs; pooled random-effects odds ratio 3.48, 95% CI 2.69-4.51
1 context sentence(design, population, supporting numbers)
Summary · context
We identified 13 phase 2 or phase 3 RCTs (1811 participants).
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4073611301
04HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with MASH and moderate-to-advanced fibrosis, pooled GLP-1 receptor agonists (especially semaglutide 2.4 mg/week) were superior to placebo for improving liver fibrosis.
In plain wordsIn adults with MASH and fibrosis, GLP-1 drugs as a group, mostly semaglutide, improved liver fibrosis more often than placebo.
Peptide
Semaglutide
Outcome
IncreaseLiver fibrosis improvement (pooled GLP-1 receptor agonists)
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
Pooled odds ratio
1.79
fibrosis improvement
Source sentences
Summary
GLP-1RAs (especially semaglutide 2.4 mg/week) for up to 72 weeks were superior to placebo in achieving MASH resolution (n = 3 RCTs; pooled random-effects odds ratio 3.48, 95% CI 2.69-4.51; I² = 0%),
1 context sentence(design, population, supporting numbers)
Summary · context
We identified 13 phase 2 or phase 3 RCTs (1811 participants).
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4073611302
05HumanNot a test of Semaglutide aloneSystematic reviewEfficacy outcome
In adults with MASLD or MASH, pooled GLP-1 receptor agonists reduced magnetic resonance-measured liver fat content, with high heterogeneity.
In plain wordsIn adults with fatty liver disease, GLP-1 drugs as a group lowered liver fat measured by scan; results varied widely between trials.
Peptide
Semaglutide
Outcome
DecreaseLiver fat content on magnetic resonance (pooled GLP-1 receptor agonists)
Study
n: not reported in source
Outcome group
Liver fat and liver function · Liver
Measurements
Pooled mean difference
−4.5%
liver fat content
Source sentences
Summary
Furthermore, GLP-1RAs reduced magnetic resonance-measured liver fat content (n = 9; pooled mean difference: -4.50%, 95% CI -6.60 to -2.40%; I² = 95.9%).
1 context sentence(design, population, supporting numbers)
Summary · context
We identified 13 phase 2 or phase 3 RCTs (1811 participants).
In this study, Semaglutide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Semaglutide.
Show in the study text Report a problemFND-4073611305

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

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
11 Oct 2026, 00:04 UTC
Study results updated
Version 1
9 Oct 2026, 03:06 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

Keywords

PepBank is a research reference. Talk to a doctor before you use any peptide.