Effects of the SGLT2 inhibitor ipragliflozin and metformin on hepatic steatosis and liver fibrosis: Sub‐analysis of a randomized controlled study

Abstract Aims To compare the effects of ipragliflozin, a sodium‐dependent glucose transporter‐2 inhibitor, and those of metformin on the visceral fat area (VFA), a prospective, multi‐centre, open‐label, blinded‐endpoint, randomized, controlled study was undertaken. The generated data were used to examine the effects of ipragliflozin and metformin on indices of hepatic steatosis and liver fibrosis. Materials and Methods In total, 103 Japanese patients with type‐2 diabetes (T2D), body mass index (BMI) of ≥22 kg/m 2 and glycated haemoglobin level of 7%–10% were randomly administered ipragliflozin 50 mg or metformin 1000 mg for 24 weeks. Various parameters, including hepatic steatosis indices, fatty liver index (FLI), hepatic steatosis index (HSI), non‐alcoholic fatty liver disease‐liver fat score (NAFLD‐LFS), liver fibrosis indices, AST to platelet ratio index (APRI) and fibrosis‐4 (FIB‐4) index, were compared in the sub‐analyses. The correlations between changes in each index and VFA were evaluated. Results At baseline, patients demonstrated moderate hepatic steatosis, with FLI scores of 52.9 ± 26.6 and 57.8 ± 29.0 in the ipragliflozin and metformin groups, respectively. At 24 weeks, compared with metformin, ipragliflozin showed improvements in hepatic steatosis indices: FLI (−9.24 ± 10.7 vs. −3.45 ± 11.8, p = 0.013), HSI (−1.45 ± 2.32 vs. −0.45 ± 1.87, p = 0.021), NAFLD‐LFS (−0.70 ± 1.46 vs. −0.04 ± 0.98, p = 0.011) and liver fibrosis index: APRI (−0.110 ± 0.323 vs. 0.033 ± 0.181, p = 0.010). In the ipragliflozin group, changes in FLI and HSI were correlated with VFA reduction ( r = 0.340, p = 0.024; r = 0.367, p = 0.011, respectively). Conclusions Compared with metformin, ipragliflozin improved multiple hepatic steatosis and liver fibrosis indices, suggesting that ipragliflozin exerts potential hepatoprotective effects in early‐stage liver disease associated with T2D.