Treating nonalcoholic steatohepatitis with antidiabetic drugs: Will GLP-1 agonists end the struggle?

Nonalcoholic fatty liver disease (NAFLD) is highly associated with insulin resistance (IR), type 2 diabetes mellitus and metabolic syndrome, being characterized as the hepatic component of metabolic syndrome. Despite its high prevalence, no pharmacological treatment has been established, as of yet. A growing body of evidence, however, shows that reducing IR can result in improvement of the biochemical and histological features of nonalcoholic steatohepatitis (NASH)-the aggressive form of NAFLD that can lead to cirrhosis and hepatocellular carcinoma. Unfortunately, the several trials that have assessed the effect of various antidiabetic agents to date have failed to establish an effective and safe treatment regimen for patients with NAFLD. Glucagon-like peptide-1 (commonly known as GLP-1) agonists are a novel class of antidiabetic drugs that improve insulin sensitivity and promote weight loss. They also appear to have a direct effect on the lipid metabolism of hepatocytes, reducing hepatic steatosis. Several trials have demonstrated that GLP-1 agonists can reduce aminotransferase levels and improve liver histology in patients with NAFLD, suggesting that these agents could serve as an alternative treatment option for these patients. This manuscript discusses the role and potential mechanisms of GLP-1 agonists in the treatment of NASH.