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
ARTICLE HIGHLIGHTS
Research 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 along with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives. This systematic review is an effort to review the available literature on the effect of sodium glucose cotransporter-2 (SGLT-2) inhibitors on NAFLD in type 2 diabetes patients.

Research motivation

Because the existing therapeutic options are not adequate for NAFLD patients, there is a need for finding newer alternatives. SGLT-2 inhibitors have shown promise in the management of NAFLD in animals. Hence, we reviewed the available literature on the effect of SGLT-2 inhibitors in NAFLD in type 2 diabetes patients. This will promote further high quality research on the effect of SGLT-2 inhibitors in NAFLD.

Research objectives

The primary outcome was the change in serum alanine aminotransferase levels in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors. The secondary outcomes were change in serum aspartate aminotransferase and gamma-glutamyl transferase levels, hepatic fat, hepatic fibrosis, metabolic profile, anthropometric parameters, and the adverse effects of SGLT-2 inhibitors.

Research methods

This systematic review was registered in PROSPERO and performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We searched PubMed/MEDLINE, Cochrane library, Google scholar, and Clinicaltrials.gov for the relevant articles to be included in this systematic review. A narrative synthesis of the results of individual studies was done. The change in the difference in means and difference in proportions and the respective P values as mentioned in the original manuscripts were tabulated and explained. The quality of the randomised controlled trials and observational studies was analysed using the Cochrane risk of bias tool and MINORS scale, respectively.

Research results

Eight articles (four randomised controlled trials and four observational studies) were included in this systematic review. A total of 214 patients were treated with SGLT-2 inhibitors. SGLT-2 inhibitors caused a significant improvement in liver enzymes, hepatic fat, hepatic fibrosis, glycaemia, insulin resistance, obesity, and lipid parameters with minimal adverse effects. However, the quality of evidence is low to moderate.

Research conclusions

We found that SGLT-2 inhibitors improved the serum levels of liver enzymes, liver fat, and liver fibrosis with additional beneficial effects on various metabolic and anthropometric parameters in type 2 diabetes patients with NAFLD. However, the number of patients treated with SGLT-2 inhibitors was small. The findings of this systematic review will have impact in choosing anti-diabetes medication like SGLT-2 inhibitors to treat NAFLD associated with type 2 diabetes.

Research perspectives

The studies included in this systematic review were heterogeneous with regard to study design and intervention drugs. Most of the studies were done amongst the Japanese population. Prospective studies, preferably randomised controlled trials, comparing different SGLT-2 inhibitors with standard treatments of NAFLD in multi-ethnic populations with a longer follow-up period are needed in the future.