Long-term luseogliflozin therapy improves histological activity of non-alcoholic steatohepatitis accompanied by type 2 diabetes mellitus

Clin J Gastroenterol. 2020 Feb;13(1):83-89. doi: 10.1007/s12328-019-01018-1. Epub 2019 Jul 10.

Abstract

A 60-year-old Japanese woman was referred to our hospital for further examination of persistent liver dysfunction. She had been suffering from type 2 diabetes mellitus since the age of 50 years. Her hemoglobin A1c (HbA1c) value was as high as 7.8% despite treatment with dipeptidyl peptidase-4 inhibitor, metformin, and sulfonylurea. After excluding viral hepatitis, alcohol or drug-induced liver injury, and autoimmune liver diseases, liver histology evidence of macrovesicular steatosis, hepatocyte ballooning, and pericellular fibrosis confirmed a diagnosis of non-alcoholic steatohepatitis (NASH). Luseogliflozin (2.5 mg/day), a sodium-glucose cotransporter 2 inhibitor (SGLT2I), was co-administered to strengthen glycemic control. Liver enzymes and HbA1c gradually improved without any adverse events. A second liver biopsy at 15 months after luseogliflozin commencement revealed improvements in steatosis, fibrosis, and overall histological activity score. This case demonstrates that long-term luseogliflozin may be a good therapeutic option for diabetic NAFLD/NASH patients. The merits of persistent SGLT2I administration for NAFLD/NASH patients warrant validation in future studies.

Keywords: Fibrosis; Luseogliflozin; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Sodium–glucose cotransporter 2 inhibitor.

Publication types

  • Case Reports

MeSH terms

  • Alanine Transaminase / metabolism
  • Aspartate Aminotransferases / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin / therapeutic use
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications
  • Non-alcoholic Fatty Liver Disease / diagnostic imaging
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Sorbitol / analogs & derivatives*
  • Sorbitol / therapeutic use
  • Sulfonylurea Compounds / therapeutic use
  • Treatment Outcome

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Sorbitol
  • Metformin
  • 1,5-anhydro-1-(5-(4-ethoxybenzyl)-2-methoxy-4-methylphenyl)-1-thioglucitol
  • Aspartate Aminotransferases
  • Alanine Transaminase