Effects of sodium glucose cotransporter 2 inhibitors and pioglitazone on FIB‐4 index in metabolic‐associated fatty liver disease

Background The antidiabetic drugs sodium glucose cotransporter 2 inhibitors (SGLT2is) and thiazolidinediones have beneficial effects on the liver dysfunction of patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus (T2DM). We aimed to determine the efficacy of these drugs for the treatment of liver disease in patients with metabolic dysfunction‐associated fatty liver disease (MAFLD) and T2DM. Methods We undertook a retrospective study of 568 patients with MAFLD and T2DM. Of these, 210 were treating their T2DM with SGLT2is (n = 95), 86 with pioglitazone (PIO), and 29 with both. The primary outcome was the change in Fibrosis‐4 (FIB‐4) index between baseline and 96 weeks. Results At 96 weeks, the mean FIB‐4 index had significantly decreased (from 1.79 ± 1.10–1.56 ± 0.75) in the SGLT2i group, but not in the PIO group. The aspartate aminotransferase to platelet ratio index, serum aspartate and alanine aminotransferase (ALT), hemoglobin A1c, and fasting blood sugar significantly decreased in both groups (ALT: SGLT2i group, −17 ± 3 IU/L; PIO group, −14 ± 3 IU/L). The bodyweight of the SGLT2i group decreased, but that of the PIO group increased (−3.2 kg and +1.7 kg, respectively). When the participants were allocated to two groups according to their baseline ALT (>30 IU/L), FIB‐4 index significantly decreased in both groups. In patients taking pioglitazone, the addition of SGLT2i improved liver enzymes but not FIB‐4 index for 96 weeks. Conclusions Treatment with SGLT2i causes a larger improvement in FIB‐4 index than PIO in patients with MAFLD over 96 weeks.