Efficacy and Safety of Empagliflozin in Metabolic Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is now the leading cause of chronic liver disease and is tightly linked to obesity, insulin resistance and type 2 diabetes. There are limited drugs approved for MASLD, creating an urgent need to repurpose agents with favourable metabolic and organ-protective profiles. Empagliflozin, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor with established cardiovascular and renal benefits, has emerged as a promising candidate, but trial-level evidence remains fragmented. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials evaluating empagliflozin in adults with imaging-confirmed MASLD or related entities. Searches of PubMed/MEDLINE, Embase, Web of Science, Scopus, and major trial registries were conducted. Continuous outcomes were pooled as mean differences (MD) using mixed-effects models. Risk of bias and certainty of evidence were formally assessed. RESULTS: Eight RCTs were included. Empagliflozin significantly reduced liver fat content (MD -2.47%, 95% CI -3.79 to -1.16) and liver stiffness (MD -0.49 kPa, 95% CI -0.89 to -0.09). Alanine aminotransferase and aspartate aminotransferase (MD -4.85 U/L, -9.21 to -0.49) declined, while aspartate aminotransferase-to-platelet ratio index improved (MD -0.03, 95% CI -0.05 to -0.00). Body mass index, visceral adipose tissue and truncal fat mass fell significantly with preservation of skeletal muscle index. Fasting glucose improved, whereas homeostatic model assessment of insulin resistance, low-density lipoprotein cholesterol, and triglycerides remained neutral. Safety profiles were consistent with established SGLT2 inhibitor experience, with no hepatic safety signals. CONCLUSION: Empagliflozin confers coherent improvements in hepatic steatosis, fibrosis surrogates, insulin resistance and visceral adiposity in MASLD, without new safety concerns, supporting its further evaluation as a potential adjunctive therapeutic option for MASLD.