Effect of empagliflozin on liver fibrosis and steatosis in patients with type 2 diabetes and non-alcoholic fatty liver disease: a randomized clinical trial

Abstract Background and aim Metabolic dysfunction-associated steatotic (MASLD) is a common complication in diabetic patients that can lead to fibrosis and severe liver complications. This study aimed to investigate the effect of empagliflozin on liver markers and fibrosis in diabetic patients with NAFLD. Methods This was a single-center, randomized, controlled, phase II clinical trial including 119 patients with type 2 diabetes and MASLD. Patients were randomized to receive either empagliflozin (10 mg or 25 mg daily) or standard care for 6 months. Liver enzymes, imaging scores (MRI and ultrasound), and fibrosis indices (FIB-4 and NFS) were assessed at baseline and at study completion. Statistical analyses included between- and within-group comparisons, adjusted models for baseline imbalances and age. Results Empagliflozin significantly reduced liver enzymes compared with controls (ALT − 41.2 vs. −4.6 IU/L; AST − 18.4 vs. −3.3 IU/L; GGT − 25.5 vs. −2.2 IU/L; all p < 0.001). The FIB-4 index decreased in the intervention group (1.20→1.06, p < 0.001) but not in controls (1.42→1.42, p = 0.233). The NAFLD fibrosis score showed no significant change. Imaging confirmed greater improvement in the empagliflozin group, with 94% showing grade 1 or lower steatosis on ultrasound and 100% achieving grade 0 on MRI (p < 0.001 for both). Importantly, complementary analyses (ANCOVA and mixed models) demonstrated that these improvements remained significant after adjustment for age and baseline values. Conclusion Empagliflozin significantly improved liver enzymes, imaging scores, and FIB-4 in patients with T2DM and MASLD. These findings support its potential as a therapeutic option in metabolic liver disease and highlight the need for longer, multicenter trials to confirm sustained benefits and to explore combination strategies with other agents. Clinical trial registration This study is related to a previously registered clinical trial conducted at Loqman-e-Hakim Hospital. The clinical trial was registered with the Iranian Registry of Clinical Trials under the number IRCT20210811052150N1.