Given that the first generation TZDs for T2DM treatment, like ciglitazone and troglitazone, were found to be highly hepatotoxic and thus showed limited clinical application and in consequence were rapidly withdrawn from the market after reports of severe liver failure and death57, a very critical point for PPARγ ligands to be considered as gold standard for T2DM drug discovery is that they did not present hepatotoxicity. This evidence concerns the gene PPARG and liver failure.