Efficacy of empagliflozin for hepatic and metabolic outcomes in adults with type 2 diabetes and MASLD/MASH (NAFLD/NASH): a systematic review, meta-analysis, and trial sequential analysis

Abstract

Patients with type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD; historically termed non-alcoholic fatty liver disease [NAFLD]) are at increased risk of advanced fibrosis. Conventional antidiabetic therapies vary in their hepatic effects and, aside from pioglitazone, provide limited direct hepatic benefit. This systematic review evaluates the efficacy of empagliflozin 10 mg, the guideline-recommended starting dose, on hepatic and metabolic outcomes in this population. We systematically searched PubMed, Scopus, Web of Science, Embase, and Cochrane Central through October 10, 2025, for randomized controlled trials (RCTs) comparing empagliflozin 10 mg versus control (placebo or active comparators). Outcomes included liver fat content, liver stiffness measurement (LSM), controlled attenuation parameter (CAP), liver enzymes, and metabolic parameters. Pooled analyses were performed using mean differences (MDs) with 95% confidence intervals (CIs) and a random-effects model. Seven RCTs ( n = 510) were included. Empagliflozin 10 mg significantly reduced CAP (MD − 19.75 dB/m, 95% CI − 36.51 to − 3.00), indicating improvement in hepatic steatosis, while no significant effect was observed on LSM (MD − 0.50 kPa, 95% CI − 1.53 to 0.54). Statistically significant reductions were observed in gamma-glutamyltransferase (GGT; MD − 16.91 IU/L, 95% CI − 22.51 to − 11.31) and, less robustly, in alanine aminotransferase (ALT; MD − 3.35 IU/L, 95% CI − 6.32 to − 0.39), with a borderline reduction in aspartate aminotransferase (AST; MD − 7.33 IU/L, 95% CI − 14.60 to − 0.06). In metabolic outcomes, empagliflozin significantly reduced body weight (MD − 4.31 kg, 95% CI − 5.56 to − 3.06), body mass index (BMI) (MD − 1.42 kg/m², 95% CI − 1.78 to − 1.07), and waist circumference (MD − 3.57 cm, 95% CI − 4.38 to − 2.75). However, no significant changes were observed in glycated hemoglobin (HbA1c) (MD − 0.24%, 95% CI − 0.72 to 0.24) or fasting plasma glucose. Empagliflozin 10 mg is associated with improvements in hepatic steatosis (CAP) and body composition in adults with T2DM and MASLD/MASH (NAFLD/NASH), whereas no significant effects were observed on liver stiffness, FIB-4, glycemic control, or the lipid profile. The evidence base is small, of short duration, and includes no histological endpoints; accordingly, no conclusions regarding antifibrotic efficacy can be drawn. Larger, longer-duration RCTs with paired histology are required.