Classical and innovative insulin sensitizing drugs for the prevention and treatment of NAFLD

Carulli, Lucia, Maurantonio, Mauro, Hebbard, Lionel, Baldelli, Enrica, Loria, Paola, and George, Jacob (2013) Classical and innovative insulin sensitizing drugs for the prevention and treatment of NAFLD. Current pharmaceutical design, 19 (29). pp. 5280-5296.

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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.


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.

Item ID: 40178
Item Type: Article (Research - C1)
ISSN: 1873-4286
Keywords: adiponectin, dipeptidyl peptidase-IV inhibitors, estrogens, glucagon-like peptide-I; hepatocellular carcinoma, insulin sensitizing drugs, metformin, nonalcoholic fatty liver disease, rimonabant, thiazolidinediones, ursodeoxycholic acid
Funders: Robert W. Storr Bequest to the Sydney Medical Foundation, National Health and Medical Research Council (NHMRC), European Community
Projects and Grants: European Community's Seventh Framework Programme (FP7/2007-2013) grant agreement no. KBBE-212399 (FishPopTrace)
Date Deposited: 27 Aug 2015 05:04
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110104 Medical Biochemistry: Lipids @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920105 Digestive System Disorders @ 100%
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