SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review

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.