In summary, we report that statin treatment i) acutely increases hepatic gluconeogenesis and blood glucose levels in mice; ii) represses Sirt6 protein expression, thereby increasing FoxO1 transactivation and gluconeogenesis genes; 3) increases miR-495, which mediates downregulation of Sirt6 protein; and finally, 4) that the hyperglycemia induced by statin was preventable by co-treatment with a Sirt6 activator. Here, SIRT6 is linked to Hyperglycemia.