Evidence map›Paper›PMID 40364529›Full record

ReviewAlimentary pharmacology & therapeutics2025

Review Article: GLP-1 Receptor Agonists and Glucagon/GIP/GLP-1 Receptor Dual or Triple Agonists-Mechanism of Action and Emerging Therapeutic Landscape in MASLD.

Maryam Zafer, Federica Tavaglione, Manuel Romero-Gómez, Rohit Loomba

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Alimentary pharmacology & therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  18. New Horizons in Metabolic Health: Unveiling the Future of Drug Discovery and Development.Endocrine, metabolic & immune disorders drug targets · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Maryam ZaferMASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA.
Federica TavaglioneMASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA.ORCID https://orcid.org/0000-0002-1720-4355
Manuel Romero-GómezUCM Digestive Diseases and Ciberehd, Virgen Del Rocío University Hospital, Institute of Biomedicine of Seville (CSIC/HUVR/US), University of Seville, Seville, Spain.ORCID https://orcid.org/0000-0001-8494-8947
Rohit LoombaMASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA.ORCID https://orcid.org/0000-0002-4845-9991

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Pediatric Trials in Non-Alcoholic Steatohepatitis (NASH)U01DK061734 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2002 to 2026
$24.4M
Tissue-specific roles of FXR in CVD and NASHP01HL147835 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2020 to 2024
$12.2M
San Diego Digestive Diseases Research CenterP30DK120515 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LARS ECKMANN, Bernd G. Schnabl · 2019 to 2026
$10.8M
HIV MASLD Clinical Research Network (HCRN)R01DK121378 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI NAGA P CHALASANI, ROHIT LOOMBA · 2020 to 2026
$8.7M
Novel IL-23 inhibitor for the treatment of alcohol associated liver diseaseU01AA029019 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KISSELEVA, TATIANA, LOOMBA, ROHIT · 2020 to 2024
$3.7M
QUS Technology for Diagnosis and Grading of Hepatic Steatosis in NAFLDR01DK106419 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT, SIRLIN, CLAUDE B · 2015 to 2019
$3.4M
San Diego Cirrhosis Clinical Research NetworkU01DK130190 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ROHIT LOOMBA · 2021 to 2026
$2.3M
Non-invasive screening of diabetics for advanced fibrosis due to NAFLDR01DK124318 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOOMBA, ROHIT · 2020 to 2022
$1.7M
John C. Martin Foundation RP124NCATS NIH HHS 5UL1TR001442NCATS NIH HHS UL1 TR001442NHLBI NIH HHS P01 HL147835NHLBI NIH HHS P01HL147835NIAAA NIH HHS U01 AA029019NIAAA NIH HHS U01AA029019NIDDK NIH HHS P30 DK120515NIDDK NIH HHS R01 DK106419NIDDK NIH HHS R01 DK121378NIDDK NIH HHS R01 DK124318NIDDK NIH HHS U01 DK061734NIDDK NIH HHS U01DK061734 U01DK130190 R01DK106419 R01DK121378NIDDK NIH HHS U01 DK130190
6 · The paper itself

Abstract

backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is primarily managed through diet and lifestyle modifications. However, these behavioural interventions alone may not achieve disease regression or remission, and maintaining long-term adherence is challenging. Incretin mimetics and other gastrointestinal hormones targeting the pleiotropic pathophysiological pathways underlying MASLD have now emerged as promising disease-modifying therapies.

aimsThis is a comprehensive review summarising the role of glucagon-like peptide-1 (GLP-1) receptor agonists and glucagon/glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor dual or triple agonists in the treatment of metabolic dysfunction-associated steatohepatitis (MASH).

methodsOnly clinical trials with endpoints assessed by liver histology were included for a robust evaluation of therapeutic efficacy.

resultsRecent evidence from phase 2 clinical trials for MASH demonstrated that pharmacological agents based on GLP-1 receptor agonism are effective in improving disease activity. Additionally, tirzepatide and survodutide showed potential clinical benefits in reducing fibrosis. Other cardiometabolic benefits observed include weight loss and improvements in glycaemic control and lipid profile. Adherence to treatment may be limited by gastrointestinal side effects, though they were found to be generally mild to moderate in severity. An interim analysis of the semaglutide phase 3 trial confirmed its efficacy in improving steatohepatitis and demonstrated its potential to improve fibrosis.

conclusionsGLP-1 receptor agonists, alone or in combination with GIP and/or glucagon receptor agonists, represent promising, effective pharmacotherapies for the treatment of MASLD/MASH. Larger and longer-duration clinical trials are needed to further evaluate the efficacy and safety of GIP receptor and glucagon receptor agonism.

Indexed as

Gastric Inhibitory PolypeptideGlucagon-Like Peptide-1 Receptor AgonistsNon-alcoholic Fatty Liver DiseaseReceptors, Gastrointestinal HormoneGlucagon-Like Peptide-1 ReceptorHumansReceptors, GlucagonGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-1 Receptor AgonistsReceptors, Gastrointestinal HormoneReceptors, GlucagonGLP‐1hepatologyMASHNAFLD/MASLD

Identifiers

PMID40364529
PMCPMC12323726

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Registered trials

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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.