Therapeutic trials in nonalcoholic steatohepatitis: Insulin sensitizers and related methodological issues

Authors

  • Vlad Ratziu,

    Corresponding author
    1. Université Pierre et Marie Curie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié Salpêtrière, INSERM UMRS 893 Paris, France
    • Université Pierre et Marie Curie, Assistance Publique Hôpitaux de Paris, Hôpital Pitié Salpêtrière, INSERM UMRS 893, 47-83 Boulevard de Hôpital, Paris Cedex 13, 75013, France
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    • fax: 33-1-42-16-14-25.

  • Stephen Caldwell,

    1. Division of GI/Hepatology, University of Virginia, Charlottesville, VA
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  • Brent A. Neuschwander-Tetri

    1. Division of Gastroenterology and Hepatology, Saint Louis University, St. Louis, MO
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  • Potential conflict of interest: V.R. is a consultant for Astellas, Axcan, Genentech, Gilead, Sanofi-Aventis and has received funding from GSK for a NASH therapeutic trial and grants from Astellas and Gilead.

Abstract

Insulin sensitizers are attractive candidate therapies for nonalcoholic steatohepatitis mainly because of the strong association between this disease and insulin resistance. This review provides a critical overview of the mechanisms of action, clinical trial results, and safety issues of metformin and glitazones in nonalcoholic steatohepatitis. It also highlights methodological challenges for trial design and proposes endpoints for future proof of principle, registrational, and postmarketing trials. (HEPATOLOGY 2010;52:2206-2215)

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