Efficacy of empagliflozin in patients with metabolic dysfunction-associated steatotic liver disease with or without diabetes: a systematic review and meta-analysis of randomized controlled trials

Background Empagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has demonstrated potential hepatic benefits in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), particularly among those with type 2 diabetes mellitus (T2DM). This meta-analysis aimed to evaluate the efficacy of empagliflozin on hepatic and metabolic outcomes in patients with MASLD. Methods A systematic literature search of PubMed, Scopus, and Web of Science was conducted up to September 2025 to identify randomized controlled trials (RCTs) evaluating empagliflozin in MASLD patients with or without T2DM. Primary outcomes included changes in liver enzymes including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatic steatosis and fibrosis indices including controlled attenuation parameter (CAP), liver stiffness measurement (LSM), aspartate aminotransferase to platelet ratio index (APRI), fibrosis-4 index (FIB-4), and the MASLD fibrosis score (NFS), and secondary outcomes included lipid parameters, glycemic control, and anthropometric measures. Results Eight RCTs involving 672 participants (353 empagliflozin and 319 placebo) were included. Empagliflozin significantly reduced ALT (mean difference MD = −9.36, 95% CI: −16.07 to −2.66, p = 0.006) and AST (MD = −9.09, 95% CI: −15.41 to −2.78, p = 0.005) compared to placebo. A significant reduction was also observed in triglyceride levels (MD = −29.29, 95% CI: −53.14 to −5.45, p = 0.02). No significant differences were found for CAP (MD = −5.72, p = 0.29), LSM (MD = −0.49, p = 0.38), APRI (MD = −0.02, p = 0.36), FIB-4 (MD = −0.06, p = 0.34), or NFS (MD = −0.04, p = 0.83). Similarly, no significant effects were observed for body weight, body mass index (BMI), fasting blood sugar, or glycated hemoglobin (HbA1c). Conclusion Empagliflozin is associated with significant improvements in liver enzyme levels and a reduction in triglyceride levels in patients with MASLD. However, no clear benefit was observed in non-invasive markers of hepatic steatosis or fibrosis. Further large-scale, long-duration RCTs with histological endpoints are needed to confirm these findings and establish empagliflozin’s role in MASLD management.