title: Classical and innovative insulin sensitizing drugs for the prevention and treatment of NAFLD.
abstract: BACKGROUND
  Nonalcoholic fatty liver disease (NAFLD), the most common chronic liver disorder worldwide, comprises a spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. NASH is associated with an increased risk of hepatocellular carcinoma (HCC) and cardiometabolic disease. Insulin resistance (IR) is the underlying pathogenic mechanism for NAFLD, the presence of which in turn, is a strong predictor for the development of metabolic disorders. Hence, therapy of NAFLD with insulin-sensitizing drugs (ISDs) should ideally improve the key hepatic histological changes (steatosis, inflammation and fibrosis), but should also reduce cardiometabolic and cancer risk.
  
  
  OBJECTIVE
  In this review, the rationale for the use of ISDs and the evidence for their efficacy are detailed. In particular, the mechanism of action, potential for use, limitations and untoward effects of metformin and thiazolidinediones are systematically reviewed. Further, we discuss novel ISDs that may have potential clinical utility in NAFLD.
  
  
  CONCLUSIONS
  Despite the theoretical prediction that ISDs might have beneficial effects on disease outcomes, evidence that ISDs are able to alter the natural history of NAFLD are presently not available. The exploration of novel strategies exploiting "nonconventional" ISDs is encouraged.
authors: Department of Internal Medicine, Endocrinology, Metabolism and Geriatrics, Nuovo Ospedale Civile Sant’Agostino-Estense of Modena, University of Modena and Reggio Emilia, Italy.
authors: Lucia
authors: L
authors: Carulli
authors: Mauro
authors: M
authors: Maurantonio
authors: Lionel
authors: L
authors: Hebbard
authors: Enrica
authors: E
authors: Baldelli
authors: Paola
authors: P
authors: Loria
authors: Jacob
authors: J
authors: George
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology; D002648:Child; D005234:Fatty Liver / Q000150:complications / Q000517:prevention & control*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000209:etiology; D008687:Metformin / Q000627:therapeutic use*; D065626:Non-alcoholic Fatty Liver Disease
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin