Effect of ipragliflozin on liver function in Japanese type 2 diabetes mellitus patients: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM)

Endocr J. 2021 Aug 28;68(8):905-918. doi: 10.1507/endocrj.EJ20-0765. Epub 2021 Apr 8.

Abstract

The STELLA-LONG TERM prospective post-marketing surveillance study assessed ipragliflozin in Japanese patients with type 2 diabetes mellitus (T2DM). This subgroup analysis of patients with liver impairment used the final 3-year results. Data on patients, adverse drug reactions (ADRs), and changes in glycemic parameters and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], gamma-glutamyl transpeptidase [γ-GTP] and alkaline phosphatase [ALP]) were collected, and the fatty liver index (FLI) was calculated. In the effectiveness analysis (n = 8,763), baseline liver function was normal in 2,605 patients (ALT <31/<21 U/L [men/women]) and abnormal in 3,277 (ALT ≥31/≥21 U/L). The abnormal liver function group had higher mean body weight and BMI than the normal liver function group (p < 0.001). In the safety analysis (n = 11,051), urinary tract infections, genital infections and hepatic disorders were more common in the abnormal than normal liver function group (2.25% vs. 1.07%; 1.78% vs. 1.14% and 1.85% vs. 1.01%). In the abnormal liver function group, there were significant (p < 0.001) decreases from baseline at 36 months in AST and ALT (from 38.8 and 53.7 U/L to 29.3 and 37.7 U/L, respectively), γ-GTP (from 75.4 to 51.7 U/L) and ALP (from 254.8 to 234.5 U/L), which were greater than in the normal liver function group. FLI reductions at 36 months were significant (p < 0.001) in subgroups with baseline FLI of ≥30 or ≥60. In conclusion, ipragliflozin improved liver function over 3 years in patients with impaired liver function, although ADRs occurred more frequently than in the normal liver function group.

Keywords: Ipragliflozin; Japan; Liver function; Post-marketing surveillance; Type 2 diabetes mellitus.

MeSH terms

  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Blood Glucose
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucosides / administration & dosage*
  • Glucosides / therapeutic use
  • Glycated Hemoglobin
  • Humans
  • Japan
  • Liver / drug effects*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Product Surveillance, Postmarketing
  • Prospective Studies
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Thiophenes / administration & dosage*
  • Thiophenes / therapeutic use
  • gamma-Glutamyltransferase / blood

Substances

  • Blood Glucose
  • Glucosides
  • Glycated Hemoglobin A
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • ipragliflozin
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase