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.
Current Pharmaceutical Design
Title:Classical and Innovative Insulin Sensitizing Drugs for the Prevention and Treatment of NAFLD
Volume: 19 Issue: 29
Author(s): Lucia Carulli, Mauro Maurantonio, Lionel Hebbard, Enrica Baldelli, Paola Loria and Jacob George
Affiliation:
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.
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Cite this article as:
Carulli Lucia, Maurantonio Mauro, Hebbard Lionel, Baldelli Enrica, Loria Paola and George Jacob, Classical and Innovative Insulin Sensitizing Drugs for the Prevention and Treatment of NAFLD, Current Pharmaceutical Design 2013; 19 (29) . https://dx.doi.org/10.2174/1381612811319290009
DOI https://dx.doi.org/10.2174/1381612811319290009 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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