The effect of ertugliflozin in patients with nonalcoholic fatty liver disease associated with type 2 diabetes mellitus: A randomized controlled trial

Medicine (Baltimore). 2024 Nov 8;103(45):e40356. doi: 10.1097/MD.0000000000040356.

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with liver inflammation, fibrosis, and cirrhosis and is associated with a greater risk of hepatocarcinoma. Nonalcoholic steatohepatitis (NASH) is a persistent and progressive form of NAFLD. Recent evidence suggested that ertugliflozin, a sodium-glucose cotransporter 2 inhibitor (SGLT2), suppresses NAFLD development in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to determine the impact of ertugliflozin on improving NAFLD in patients with T2DM and the function of liver enzymes.

Methods: This prospective, randomized, double-blind, placebo-controlled, interventional study aimed to determine the effectiveness of 15 mg of ertugliflozin versus 30 mg of the standard therapy pioglitazone versus placebo in NAFLD patients with T2DM. The study was established based on patient randomization in three groups: ertugliflozin, pioglitazone, and a placebo. This study was registered under the Australian New Zealand Clinical Trial Registry (Trial ID: ACTRN12624000032550).

Results: The impact of therapy was determined in the treatment groups by utilizing liver ultrasonography and biochemical parameters. After 24 weeks of clinical study, the results revealed significant improvement in the grades of fatty liver, especially in the ertugliflozin group. The number of patients with hepatic steatosis significantly decreased among the respective groups classified according to fatty liver grade. Among patients in the ertugliflozin and pioglitazone groups, 45% to 23.4% and 41.7% to 26.6%, respectively, decreased in the Grade 2 group. The aspartate aminotransferase and alanine aminotransferase levels were significantly lower in all the study groups, especially in the ertugliflozin group (P ≤ .001).

Conclusion: The present study revealed that the concomitant use of ertugliflozin has favorable effects on liver enzymes, as it decreases liver fat intake and reduces complications in patients with NAFLD-associated T2DM. However, more in-depth studies will be required to observe every aspect of ertugliflozin.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Double-Blind Method
  • Female
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Liver / diagnostic imaging
  • Liver / drug effects
  • Liver / pathology
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease* / complications
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Pioglitazone* / therapeutic use
  • Prospective Studies
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • ertugliflozin
  • Bridged Bicyclo Compounds, Heterocyclic
  • Sodium-Glucose Transporter 2 Inhibitors
  • Pioglitazone
  • Hypoglycemic Agents
  • Alanine Transaminase