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

doi:10.4239/wjd.v12.i1.84

Novel glucose-lowering drugs for non-alcoholic fatty liver disease

World J Diabetes. 2021 Jan 15;12(1):84-97. doi: 10.4239/wjd.v12.i1.84.

Authors

Zuo-Di Fu¹, Xiao-Ling Cai², Wen-Jia Yang², Ming-Ming Zhao³, Ran Li⁴, Yu-Feng Li⁵

Affiliations

¹ Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Beijing 101200, China.
² Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
³ The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing 100079, China.
⁴ Sport Science School, Beijing Sport University, Beijing 100078, China.
⁵ Department of Endocrinology, Beijing Friendship Hospital Pinggu Campus, Capital Medical University, Beijing 101200, China. yflee@bjmu.edu.cn.

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