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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.

作者信息

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

机构信息

MASLD Research Center, Division of Gastroenterology and Hepatology, University of California at San Diego, La Jolla, California, USA.

UCM Digestive Diseases and Ciberehd, Virgen Del Rocío University Hospital, Institute of Biomedicine of Seville (CSIC/HUVR/US), University of Seville, Seville, Spain.

出版信息

Aliment Pharmacol Ther. 2025 Jun;61(12):1872-1888. doi: 10.1111/apt.70196. Epub 2025 May 13.


DOI:10.1111/apt.70196
PMID:40364529
Abstract

BACKGROUND: Metabolic 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. AIMS: This 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). METHODS: Only clinical trials with endpoints assessed by liver histology were included for a robust evaluation of therapeutic efficacy. RESULTS: Recent 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. CONCLUSIONS: GLP-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.

摘要

相似文献

[1]
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.

Aliment Pharmacol Ther. 2025-6

[2]
The quantity, quality and findings of network meta-analyses evaluating the effectiveness of GLP-1 RAs for weight loss: a scoping review.

Health Technol Assess. 2025-6-25

[3]
Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver.

J Hepatol. 2023-12

[4]
Glucagon-Like Peptide-1 Receptor Agonists Improve MASH and Liver Fibrosis: A Meta-Analysis of Randomised Controlled Trials.

Liver Int. 2025-9

[5]
Plain language summary about GLP-1 treatments in people with metabolic dysfunction-associated steatotic liver disease.

Postgrad Med. 2025-7-30

[6]
Pharmacological treatment options for metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus: A systematic review.

Eur J Clin Invest. 2025-4

[7]
GLP-1, GIP/GLP-1, and GCGR/GLP-1 receptor agonists: Novel therapeutic agents for metabolic dysfunction-associated steatohepatitis.

World J Gastroenterol. 2024-12-28

[8]
Comparative efficacy of THR-β agonists, FGF-21 analogues, GLP-1R agonists, GLP-1-based polyagonists, and Pan-PPAR agonists for MASLD: A systematic review and network meta-analysis.

Metabolism. 2024-12

[9]
A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis.

N Engl J Med. 2024-7-25

[10]
Management of type 2 diabetes with the dual GIP/GLP-1 receptor agonist tirzepatide: a systematic review and meta-analysis.

Diabetologia. 2022-8

引用本文的文献

[1]
Multifaceted Human Antigen R (HuR): A Key Player in Liver Metabolism and MASLD.

Livers. 2025-9

[2]
Exploring the role of xanthine oxidase and aldehyde oxidase in metabolic dysfunction-associated steatotic liver disease (MASLD).

J Mol Histol. 2025-7-23

本文引用的文献

[1]
Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.

N Engl J Med. 2025-6-5

[2]
Metabolic dysfunction-associated steatotic liver disease in adults.

Nat Rev Dis Primers. 2025-3-6

[3]
FDA Approves Semaglutide to Reduce Risk of Kidney Disease Progression.

JAMA. 2025-2-28

[4]
Glucagon-Like Peptide-1 Receptor Agonists and Liver Outcomes in Patients With MASLD and Type 2 Diabetes.

Aliment Pharmacol Ther. 2025-4

[5]
Therapeutic Potential of Glucagon-like Peptide-1 Receptor Agonists in Obstructive Sleep Apnea Syndrome Management: A Narrative Review.

Diseases. 2024-9-23

[6]
GLP-1 Receptor Agonists and Risk for Cirrhosis and Related Complications in Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

JAMA Intern Med. 2024-11-1

[7]
Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials.

Lancet. 2024-9-7

[8]
Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial.

Lancet. 2024-8-24

[9]
The benefits of GLP-1 drugs beyond obesity.

Science. 2024-7-19

[10]
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

Nat Med. 2024-7

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