Long‐term effects of ipragliflozin and pioglitazone on metabolic dysfunction‐associated steatotic liver disease in patients with type 2 diabetes: 5 year observational follow‐up of a randomized, 24 week, active‐controlled trial

Abstract

ABSTRACT Aims/Introduction We conducted a 5 year post‐trial monitoring study of our previous randomized 24 week, open‐label, active‐controlled trial that showed beneficial effects of ipragliflozin on metabolic dysfunction‐associated steatotic liver disease (MASLD), identical to those of pioglitazone. Materials and Methods In our previous trial, 66 patients with MASLD and type 2 diabetes were randomly assigned to receive either ipragliflozin (n = 32) or pioglitazone (n = 34). Upon its conclusion, 61 patients were monitored for 5 years for outcome measures of MASLD, glycemic, and metabolic parameters. Differences between the two groups were analyzed at baseline, 24 weeks, and 5 years; changes in outcome measures from baseline were also evaluated. Results At 5 years, the mean liver‐to‐spleen attenuation ratio increased by 0.20 (from 0.78 ± 0.24 to 0.98 ± 0.20) in the ipragliflozin group and by 0.26 (from 0.76 ± 0.26 to 1.02 ± 0.20) in the pioglitazone group (P = 0.363). Similarly, ipragliflozin and pioglitazone significantly improved serum aminotransferase, HbA1c, and fasting plasma glucose levels over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat area observed at 24 weeks were sustained throughout the 5 years (−4.0%, P = 0.0075 and −7.6%, P = 0.045, respectively). Moreover, ipragliflozin significantly reduced the values of fibrosis markers (serum ferritin and FIB‐4 index), was well tolerated, and had a higher continuation rate for 5 years compared with pioglitazone. Conclusions Ipragliflozin and pioglitazone improved MASLD and glycemic parameters over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat mass persisted for 5 years.

Keywords

• Metabolic dysfunction‐associated steatotic liver disease
• Non‐alcoholic fatty liver disease
• Sodium‐glucose cotransporter 2 inhibitors