An Update on the Effect Of Sodium Glucose Cotransporter 2 Inhibitors on Non-Alcoholic Fatty Liver Disease: A Systematic Review of Clinical Trials

Abstract

Non-alcoholic fatty liver disease (NAFLD) is one of the main causes of liver disease, specifically chronic liver disease. Type 2 diabetes (T2DM) is associated with the risk of NAFLD given that patients usually have insulin resistance as one of the observed complications with NAFLD. Hypoglycemic agents, including sodium glucose cotransporter 2 (SGLT-2), have shown to improve NAFLD. The objective of this study is to evaluate the effect of SGLT-2 inhibitors on NAFLD patients' outcomes, whether they have T2DM or not. We conducted a comprehensive search using the PubMed and Ovid databases to identify published studies that addressed the use of SGLT-2 inhibitors in NAFLD patients. The outcomes assessed include changes in liver enzymes, lipid profiles, weight changes, the fibrosis-4-index (FIB4), and magnetic resonance imaging proton density-based fat fraction (MRI-PDFF). Only clinical trials that met the quality measures were included in this review. Out of 382 potential studies, we included 16 clinical trials that discussed the use of SGLT-2 inhibitors in NAFLD patients. A total of 753 patients were enrolled in these trials. The majority of the trials reported positive effects of SGLT-2 inhibitors on liver enzymes; alanine transaminase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase. All 10 trials that reported changes in body mass index (BMI) from baseline showed a statistically significant reduction with SGLT-2 inhibitor use, while 11 studies reported a significant increase in high density lipoprotein (HDL) levels, 3 studies reported a reduction in triglycerides (TG) levels, and 2 studies showed a decrease in low density lipoprotein (LDL) levels. The available evidence shows that the use of SGLT-2 inhibitors in NAFLD is associated with positive outcomes on liver enzymes, lipid profiles, and BMI. Further studies with larger sample size and longer follow-up time are warranted.

Keywords: diabetes; nonalcoholic fatty liver disease; nonalcoholic steatohepatitis; sodium glucose cotransporter 2 inhibitors; systematic review; type 2 diabetes mellitus.