Insulin sensitizers for the treatment of non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disease in the Western world and is closely associated with metabolic syndrome, which includes hypertension, central obesity, dyslipidemia and insulin resistance. NAFLD includes a wide spectrum of liver alterations, ranging from simple hepatic steatosis to variable degrees of fibrosis, cirrhosis and even hepatocellular carcinoma. Although the etiology and progression of the disorder remain poorly understood, insulin resistance is considered to play a pivotal role in the pathogenesis. Insulin sensitizers such as biguanides, thiazolidinediones (TZDs), glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have been studied as therapeutic approaches for NAFLD in recent years. Metformin improves insulin sensitivity and serum alanine transaminase and aspartate transaminase (ALT/AST) levels in the majority of subjects; however, it has no significant effect on liver histology. TZDs improve insulin sensitivity, serum ALT/AST levels and histology in some cases, but there are some concerns about the safety of long-term therapy. Selection of appropriate patients for avoiding side effects and the treatment of underlying disease are the main points. These drugs are the best choice for the treatment of NAFLD in patients with type 2 DM who are also candidates for treatment with an insulin sensitizer. The present review provides an overview of insulin sensitizers in the treatment of NAFLD.

Keywords: Insulin sensitizers; Metformin; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Thiazolidinediones

Core tip: Non-alcoholic fatty liver disease (NAFLD) is increasing significantly due to the obesity epidemic. Insulin resistance, mainly caused by obesity, plays a primary role in NAFLD pathogenesis. Medications that improve insulin sensitivity are theorized to be useful in the treatment of NAFLD. Therefore, recent studies have explored the role of insulin sensitizers to improve biochemical and histological features of NAFLD.