Letter to the Editor
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2024; 30(48): 5205-5211
Published online Dec 28, 2024. doi: 10.3748/wjg.v30.i48.5205
GLP-1, GIP/GLP-1, and GCGR/GLP-1 receptor agonists: Novel therapeutic agents for metabolic dysfunction-associated steatohepatitis
Anmol Singh, Aalam Sohal, Akash Batta
Anmol Singh, Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
Aalam Sohal, Division of Gastroenterology, Creighton University School of Medicine, Phoenix, AZ 85012, United States
Akash Batta, Department of Cardiology, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
Author contributions: Sohal A and Batta A designed the Editorial; Singh A and Sohal A performed the literature review and data collection; Batta A supervised the study and provided key feedback and suggestions; Singh A and Batta A analyzed the data and wrote the manuscript and subsequently revised it; all authors have read and approved the final manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Akash Batta, DM, MD, Academic Editor, Academic Research, Assistant Professor, Department of Cardiology, Dayanand Medical College and Hospital, Tagore Nagar, Civil Lines, Ludhiana 141001, Punjab, India. akashbatta02@gmail.com
Received: August 27, 2024
Revised: October 24, 2024
Accepted: November 12, 2024
Published online: December 28, 2024
Processing time: 94 Days and 15.9 Hours
Abstract

The global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is estimated at 32.4%, reflecting its growing clinical significance. MASLD, which includes MASLD and metabolic dysfunction-associated steatohepatitis (MASH) has been linked to increased metabolic, cardiovascular, and malignant morbidity. Progression into fibrotic stages of MASLD is also strongly associated with liver-related mortality. The past few years have seen a heightened focus on creating innovative therapeutic strategies for MASH management. GLP-1 receptor agonists (RA) have also emerged as a potential treatment option. Studies on GLP-1 agonists, such as liraglutide and semaglutide, have demonstrated efficacy in MASH management, albeit with limited histological improvement of fibrosis. However, recent investigations into GLP-1/GIP RA (tirzepatide) and Glucagon/GLP-1 RA (survodutide) have shown even more encouraging results, with higher rates of MASH resolution and fibrosis improvement. The tolerability of these medications due to their gastrointestinal side effects remains a major concern. Future research should focus on optimizing drug regimens, identifying patients most likely to benefit, and balancing efficacy with tolerability. The evolving landscape of MASH therapeutics suggests a bright future, with the potential for combination therapies to further enhance patient outcomes.

Keywords: Glucagon-like peptide-1 receptor agonists; Metabolic dysfunction-associated steatotic liver disease; Metabolic dysfunction-associated steatohepatitis; Liver fibrosis; Semaglutide; Tirzepatide; Survodutide

Core Tip: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 1/3rd of the global population, leading to significant morbidity and mortality. GLP-1 agonists may decrease the risk of progression of MASLD by reducing fatty acid oxidation and cytokine production. GLP-1/GIP receptor agonists (RA) (tirzepatide) and Glucagon/GLP-1 RA (survodutide, efinopegdutide and pemvidutide), have also shown promising results in resolving metabolic dysfunction-associated steatohepatitis (MASH) and demonstrating histological improvement in liver fibrosis. The advancing field of MASH management points to a promising future, with combination therapies likely to significantly improve patient outcomes.