Classical and Innovative Insulin Sensitizing Drugs for the Prevention and Treatment of NAFLD

Author(s): Lucia Carulli , Mauro Maurantonio , Lionel Hebbard , Enrica Baldelli , Paola Loria , Jacob George .

Journal Name: Current Pharmaceutical Design

Volume 19 , Issue 29 , 2013

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.

Objectives. 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.

Results and Conclusion. 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.

Keywords: Adiponectin; dipeptidyl peptidase-IV inhibitors; estrogens; glucagon-like peptide-1; hepatocellular carcinoma; insulin sensitizing drugs; metformin; nonalcoholic fatty liver disease; rimonabant; thiazolidinediones; ursodeoxycholic acid.

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Article Details

VOLUME: 19
ISSUE: 29
Year: 2013
Page: [5280 - 5296]
Pages: 17
DOI: 10.2174/1381612811319290009
Price: $58

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