Empagliflozin Treatment for Non-alcoholic Fatty Liver Disease in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Abstract

Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has emerged as a promising therapeutic option for patients with concurrent type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). This systematic review and meta-analysis evaluated the efficacy of empagliflozin on liver enzymes and metabolic parameters in this dual-pathology population. A comprehensive search was conducted across PubMed/MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases from inception to July 2025. Randomized controlled trials (RCTs) comparing empagliflozin with placebo in adults with T2DM and NAFLD were included. Primary outcomes included changes in liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT)), while secondary outcomes comprised systolic blood pressure (SBP) and glycated hemoglobin (HbA1c) levels. Four studies met the inclusion criteria, encompassing 393 participants (206 empagliflozin, 187 control) with follow-up periods ranging from 20 to 24 weeks. Meta-analysis demonstrated significant reductions in ALT (mean difference (MD): -11.61; 95% confidence interval (CI): -19.18 to -4.04), AST (MD: -10.31; 95% CI: -15.41 to -5.21), and GGT levels (MD: -15.19; 95% CI: -18.13 to -12.25) with empagliflozin treatment compared to placebo. However, no statistically significant differences were observed for SBP (MD: -0.87; 95% CI: -7.93 to 6.20) or HbA1c (MD: -0.44; 95% CI: -1.10 to 0.22). Considerable heterogeneity was noted across studies for most outcomes. These findings suggest that empagliflozin offers hepatoprotective benefits in patients with concurrent T2DM and NAFLD, primarily through significant improvements in liver enzyme profiles. However, larger long-term studies with histological endpoints are needed to establish definitive clinical recommendations for this therapeutic approach.