Meta-Analysis
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2021; 12(1): 84-97
Published online Jan 15, 2021. doi: 10.4239/wjd.v12.i1.84
Novel glucose-lowering drugs for non-alcoholic fatty liver disease
Zuo-Di Fu, Xiao-Ling Cai, Wen-Jia Yang, Ming-Ming Zhao, Ran Li, Yu-Feng Li
Zuo-Di Fu, Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Beijing 101200, China
Xiao-Ling Cai, Wen-Jia Yang, Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing 100044, China
Ming-Ming Zhao, The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100079, China
Ran Li, Sport Science School, Beijing Sport University, Beijing 100078, China
Yu-Feng Li, Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Capital Medical University, Beijing 101200, China
Author contributions: Li YF, Zhao MM, and Li R conceived and designed the review; Fu ZD, Cai XL, and Yang WJ provided statistical analysis and drafted the manuscript. All authors read and approved the final manuscript.
Supported by The Capital's Funds for Health Improvement and Research, No. CFH2020-2-7131.
Conflict-of-interest statement: We declare no competing interests.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu-Feng Li, MD, Chief Doctor, Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Captital Medical University, No. 59 North Xinping Road, Beijing 101200, China. yflee@bjmu.edu.cn
Received: September 21, 2020
Peer-review started: September 21, 2020
First decision: November 16, 2020
Revised: November 22, 2020
Accepted: December 2, 2020
Article in press: December 2, 2020
Published online: January 15, 2021
Abstract
BACKGROUND

The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease (NAFLD) is unknown.

AIM

To evaluate the efficacy of glucose-lowering drugs dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter 2 (SGLT2) inhibitors in treating NAFLD and to perform a comparison between these treatments.

METHODS

Electronic databases were systematically searched. The inclusion criteria were: Randomized controlled trials comparing DPP-4 inhibitors, GLP-1 RAs, or SGLT2 inhibitors against placebo or other active glucose-lowering drugs in NAFLD patients, with outcomes of changes in liver enzyme [alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)] from baseline.

RESULTS

Nineteen studies were finally included in this meta-analysis. Compared with placebo or other active glucose-lowering drug treatment, treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors all led to a significant decrease in ALT change and AST change from baseline. The difference between the DPP-4 inhibitor and SGLT2 inhibitor groups in ALT change was significant in favor of DPP-4 inhibitor treatment (P < 0.05). The trends of reduction in magnetic resonance imaging proton density fat fraction and visceral fat area changes were also observed in all the novel glucose-lowering agent treatment groups.

CONCLUSION

Treatment with DPP-4 inhibitors, GLP-1 RAs, and SGLT2 inhibitors resulted in improvements in serum ALT and AST levels and body fat composition, indicating a beneficial effect in improving liver injury and reducing liver fat in NAFLD patients.

Keywords: Non-alcoholic fatty liver disease, Glucose-lowering drug, Meta-analysis, Dipeptidyl peptidase-4 inhibitor, Sodium-glucose cotransporter 2 inhibitor, Glucagon-like peptide-1 receptor agonist

Core Tip: The efficacy of novel glucose-lowering drugs in treating non-alcoholic fatty liver disease is unknown. The results of this meta-analysis showed that treatment with dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors resulted in improvements in serum alanine aminotransferase and aspartate aminotransferase levels, indicating a beneficial effect in the improvement of liver injury.