Role of SGLT-2 Inhibitors in Treatment of Patients with Type 2 Diabetes and NAFLD

: The role of sodium-glucose cotransporters-2 (SGLT-2) inhibitors in treatment of non-alcoholic fatty liver disease (NAFLD) is unclear. Objective: To examine the possible therapeutic role of SGLT-2 inhibitors in patients with type 2 diabetes and NAFLD. Methods: Pubmed search of English literature up to February 17, 2022. Search terms are fatty liver, SGLT-2, sodium-glucose cotransporter-2 inhibitors, diabetes, weight loss, liver biopsy. Randomized studies are reviewed with focus placed on doubleblind, placebo-controlled trials. Meta-analyses and pertinent reviews are also included. Results: Six randomized double-blind placebo-controlled trials examined the effects of SGLT-2 inhibitors on intra-hepatic fat content (IHFC) over 8-24 weeks mostly by magnetic resonance imaging (MRI) techniques. Two trials reported significant reduction in IHFC with SGLT-2 inhibitors, one reported borderline statistically significant reduction, and the remaining 3 trials showed a trend towards amelioration of IHFC that did not reach statistical significance. One placebo-controlled study showed that empagliflozin (10 mg/d) may decrease IHFC in patients with NAFLD without diabetes. Weight loss induced by SGLT-2 inhibitors appears to be a major factor in decreasing IHFC. Two small non-randomized biopsy studies showed that canagliflozin could improve histopathologic disease severity in patients with confirmed NAFLD and type 2 diabetes.