Systematic Reviews
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Feb 15, 2019; 10(2): 114-132
Published online Feb 15, 2019. doi: 10.4239/wjd.v10.i2.114
SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review
Henith Raj, Harsh Durgia, Rajan Palui, Sadishkumar Kamalanathan, Sandhiya Selvarajan, Sitanshu Sekhar Kar, Jayaprakash Sahoo
Henith Raj, Harsh Durgia, Rajan Palui, Sadishkumar Kamalanathan, Jayaprakash Sahoo, Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Sandhiya Selvarajan, Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Sitanshu Sekhar Kar, Department of Preventive and Social Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
Author contributions: Raj H, Durgia H, and Palui R designed the work; Kamalanathan SK, Selvarajan S, Kar SS, and Sahoo JP interpreted the data; Raj H, Durgia H, and Palui R revised it critically for important intellectual content; Kamalanathan SK, Selvarajan S, Kar SS, and Sahoo JP drafted the work; all authors approved the final version of the manuscript.
Conflict-of-interest statement: All authors have no conflicts of interest to report.
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 which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: Jayaprakash Sahoo, MD, DM, Associate Professor, Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education and Research, Room No. 5444, the 4th Floor, Superspeciality block, Puducherry 605006, India. jayaprakash.s@jipmer.edu.in
Telephone: +91-9629158368
Received: October 5, 2018
Peer-review started: October 6, 2018
First decision: November 15, 2018
Revised: December 14, 2018
Accepted: December 29, 2018
Article in press: December 30, 2018
Published online: February 15, 2019
Processing time: 136 Days and 14.8 Hours
Abstract
BACKGROUND

Non-alcoholic fatty liver disease (NAFLD) is a common comorbidity with type 2 diabetes. The existing therapeutic options for NAFLD are not adequate. Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD. Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis. The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.

AIM

To assess the effect of sodium glucose cotransporter-2 (SGLT-2) inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.

METHODS

We searched PubMed/MEDLINE, Cochrane library, Google scholar, and Clinicaltrials.gov for the relevant articles to be included in this systematic review. Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included. Data from eight studies (four randomised controlled trials and four observational studies) were extracted and a narrative synthesis was done. A total of 214 patients were treated with SGLT-2 inhibitors in these studies (94 in randomised controlled trials and 120 in observational studies).

RESULTS

The primary outcome measure was change in serum alanine aminotransferase level. Out of eight studies, seven studies showed a significant decrease in serum alanine aminotransferase level. Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase. Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors. Likewise, among the three studies that evaluated a change in indices of hepatic fibrosis, two studies revealed a significant improvement in liver fibrosis. Moreover, there was an improvement in obesity, insulin resistance, glycaemia, and lipid parameters in those subjects taking SGLT-2 inhibitors. The studies disclosed that about 17% (30/176) of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40% (10/23) of them had genitourinary tract infections.

CONCLUSION

Based on low to moderate quality of evidence, SGLT-2 inhibitors improve the serum level of liver enzymes, decrease liver fat, and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.

Keywords: Alanine aminotransferase; Hepatic fat; Hepatic fibrosis; Non-alcoholic fatty liver disease; Sodium-glucose cotransporter-2 inhibitor; Type 2 diabetes mellitus

Core tip: The frequent coexistence of non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, their adverse health consequences, and lack of adequate therapeutic options makes it necessary to search for newer alternatives. Currently, pioglitazone and vitamin E are recommended in addition to lifestyle modifications for the management of NAFLD. Animal studies have shown that sodium glucose cotransporter-2 inhibitors might be beneficial in NAFLD present in diabetes patients. The current systematic review shows that sodium glucose cotransporter-2 inhibitors improve the serum level of liver enzymes, liver fat, and liver fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.