Letter to the Editor
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2023; 29(48): 6235-6238
Published online Dec 28, 2023. doi: 10.3748/wjg.v29.i48.6235
Potential therapeutic targets for nonalcoholic fatty liver disease: Glucagon-like peptide 1
Yue-Hua Yin, Li-Xuan Sang, Bing Chang
Yue-Hua Yin, Bing Chang, Department of Gastroenterology, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Li-Xuan Sang, Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110022, Liaoning Province, China
Author contributions: Yin YH, Sang LX and Chang B wrote this letter.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: Bing Chang, Chief Physician, Postdoc, Professor, Department of Gastroenterology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning Province, China. cb000216@163.com
Received: October 7, 2023
Peer-review started: October 7, 2023
First decision: October 23, 2023
Revised: November 8, 2023
Accepted: December 6, 2023
Article in press: December 6, 2023
Published online: December 28, 2023
Processing time: 81 Days and 3.3 Hours
Abstract

Nonalcoholic fatty liver disease (NAFLD) is the most rapidly growing contributor to liver mortality and morbidity. Hepatocellular injury in nonalcoholic steatohepatitis (NASH) is caused by an increase in metabolic substrates (glucose, fructose, and fatty acids), leading fatty acids to participate in pathways that cause cellular injury and a poor response to injury. The pathogenesis of this disease is largely associated with obesity, type 2 diabetes, and increasing age. To date, there are no Food and Drug Administration-approved treatments for NAFLD/NASH or its associated fibrosis. Since one of the pathogenic drivers of NASH is insulin re-sistance, therapies approved for the treatment of type 2 diabetes are being evaluated in patients with NASH. Currently, the glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide is a safe, well-studied therapeutic for NAFLD/ NASH patients. Existing research demonstrates that semaglutide can increase the resolution of NASH but not improve fibrosis. However, improving the fibrosis of NAFLD is the only way to improve the long-term prognosis of NAFLD. Given the complex pathophysiology of NASH, combining therapies with complementary mechanisms may be beneficial. Researchers have conducted trials of semaglutide in combination with antifibrotic drugs. However, the results have not fully met expectations, and it cannot be ruled out that the reason is the short trial time. We should continue to pay increasing attention to GLP-1RAs.

Keywords: Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis; Antidiabetic drugs; Glucagon-like peptide 1; Semaglutide

Core Tip: Semaglutide is effective and safe for nonalcoholic fatty liver disease (NAFLD) but does not improve fibrosis. The treatment of NAFLD requires further combinations of drugs with different and complementary mechanisms of action.