Comparative Analysis of Glucagon Receptor Agonists vs. Resmetirom in MASLD and MASH: Network Meta-Analysis of Clinical Trials.

Andonie CR, Abusalameh A, Ismail I, Hodrob T, Ladadweh M, Ayesh H

Endocrinology, diabetes & metabolism1 Jan 2026Cited by 1 (Europe PMC)

PMID41466530PMCIDPMC12750095DOI10.1002/edm2.70157PepBankPUB-41466530

Summary

BackgroundMASLD and its progressive form MASH represent a global public health challenge due to their rising prevalence and their possible progression to cirrhosis and HCC. Resmetirom, dual (e.g., cotadutide, survodutide), and triple GRAs (e.g., retarutide) have demonstrated potential efficacy in recent clinical trials. This network meta-analysis evaluates the comparative efficacy and safety of these treatments.MethodsWe systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH. The outcomes assessed included changes in ALT, AST, LDL, and HDL levels, changes in MRI-PDFF, safety outcomes (diarrhoea, fatigue, and nausea), serious adverse events, ELF, adiponectin, and MASH resolution with no worsening of fibrosis. Random-effects model and network meta-analysis methods were employed.ResultsSix trials met the inclusion criteria. GRAs significantly reduced ALT levels with MD of -22.10, while resmetirom demonstrated the greatest reduction in AST levels with a MD of -13.17. Resmetirom also led to a borderline significant increase in HDL with the most significant reduction in LDL levels. Moreover, GRAs showed a significant effect on MRI-PDFF with a MD of -46.09. Overall, resmetirom showed a more favourable safety profile. In addition, GRAs significantly decreased ELF scores, resmetirom significantly improved MASH resolution without worsening of fibrosis, and both treatments significantly increased adiponectin.ConclusionGRAs superiorly reduce ALT levels, MRI-PDFF, and ELF. Resmetirom significantly reduces AST, HDL, and LDL levels, increases MASH resolution without worsening of fibrosis, and offers a more favourable safety profile. Both GRAs and resmetirom significantly increase adiponectin.

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

Results from this study5

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone5

In this study, Survodutide 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 Survodutide.

01HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of adults with MASLD and MASH, glucagon receptor agonists (a class that includes survodutide) lowered ALT levels, with a mean difference of -22.10.
In plain wordsIn a pooled analysis of adults with fatty liver, a drug class that includes survodutide lowered the enzyme ALT. This is not survodutide alone.
Peptide
Survodutide
Outcome
DecreaseALT change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
ALT mean difference
−22.1
glucagon receptor agonists
Source sentences
Summary
GRAs significantly reduced ALT levels with MD of -22.10
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4146653001
02HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of adults with MASLD and MASH, glucagon receptor agonists (a class that includes survodutide) significantly reduced liver fat on MRI-PDFF, with a mean difference of -46.09.
In plain wordsIn a pooled analysis of adults with fatty liver, a drug class that includes survodutide lowered liver fat on MRI. This is not survodutide alone.
Peptide
Survodutide
Outcome
DecreaseMRI-PDFF change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Measurements
MRI-PDFF mean difference
−46.09
glucagon receptor agonists
Source sentences
Summary
Moreover, GRAs showed a significant effect on MRI-PDFF with a MD of -46.09.
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4146653002
03HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of adults with MASLD and MASH, glucagon receptor agonists (a class that includes survodutide) significantly decreased Enhanced Liver Fibrosis (ELF) scores.
In plain wordsIn a pooled analysis of adults with fatty liver, a drug class that includes survodutide lowered a liver scarring score. This is not survodutide alone.
Peptide
Survodutide
Outcome
DecreaseELF score change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Liver fat and liver function · Liver
Source sentences
Summary
GRAs significantly decreased ELF scores
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4146653003
04HumanNot a test of Survodutide aloneSystematic reviewEfficacy outcome
In a network meta-analysis of adults with MASLD and MASH, glucagon receptor agonists (a class that includes survodutide) and resmetirom both significantly increased adiponectin.
In plain wordsIn a pooled analysis of adults with fatty liver, a drug class that includes survodutide raised adiponectin. This is not survodutide alone.
Peptide
Survodutide
Outcome
IncreaseAdiponectin change
Study
n: not reported in source
Comparator
Placebo
Outcome group
Inflammation markers · Metabolic and weight
Source sentences
Summary
both treatments significantly increased adiponectin.
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4146653004
05HumanNot a test of Survodutide aloneSystematic reviewSafety outcome
In a network meta-analysis of adults with MASLD and MASH, resmetirom showed a more favourable overall safety profile than the glucagon receptor agonists.
In plain wordsIn a pooled analysis of adults with fatty liver disease, resmetirom had a better overall safety profile than drugs of the survodutide class.
Peptide
Survodutide
Outcome
Direction not reportedOverall safety profile versus resmetirom
Study
n: not reported in source
Comparator
Resmetirom
Outcome group
Adverse events · Whole body
Source sentences
Summary
Overall, resmetirom showed a more favourable safety profile.
1 context sentence(design, population, supporting numbers)
Summary · context
We systematically searched PubMed, Scopus, ClinicalTrials.gov, and Cochrane Central for randomised controlled trials evaluating these medications versus placebo in adults with MASLD and MASH.
In this study, Survodutide 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 Survodutide.
Show in the study text Report a problemFND-4146653005

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
9 Oct 2026, 19:08 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

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