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. © 2026 Elsevier Masson SAS