Quantitative effects of sodium-glucose cotransporter-2 inhibitors on liver functions in patients with nonalcoholic fatty liver disease

Expert Rev Clin Pharmacol. 2023 Jul-Dec;16(10):991-998. doi: 10.1080/17512433.2023.2256224. Epub 2023 Sep 11.

Abstract

Background: The present study aimed to explore the quantitative effects of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on liver functions in patients with nonalcoholic fatty liver disease (NAFLD).

Research design and methods: A total of 4771 patients with NAFLD were included for analysis by means of nonlinear mixed effect modeling, where the change rates of liver functions were taken as the evaluation indexes so as to eliminate the potential baseline effects.

Results: For ALT and AST, the Emax of SGLT-2 inhibitors was -17.8% and -13.9%, respectively, and the ET50 was 6.86 weeks and 10 weeks, respectively. Furthermore, the duration time to achieve 25%, 50%, 75%, and 80% Emax were 2.3 weeks, 6.86 weeks, 20.6 weeks, 27.5 weeks in ALT, 3.4 weeks, 10 weeks, 30 weeks, 40 weeks in AST, respectively. Thus, to realize the plateau period (80% of Emax) of SGLT-2 inhibitors on ALT and AST in patients with NAFLD, 100 mg/day canagliflozin (or 10 mg/day dapagliflozin or 10 mg/day empagliflozin) needs to be taken for 20.6 weeks and 30 weeks, respectively.

Conclusions: The present study explored the quantitative effects of SGLT-2 inhibitors on liver functions and recommends a therapeutic regimen in patients with NAFLD.

Keywords: Quantitative effects; liver functions; nonalcoholic fatty liver disease; sodium-glucose cotransporter-2 inhibitors; therapeutic regimen recommendation.

MeSH terms

  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucose
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Sodium
  • Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Hypoglycemic Agents
  • Glucose
  • Sodium