Modulation of glucose homeostasis by administration of ciclopirox (6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one) is described. Methods can be utilized in treatment of conditions that involve loss of glucose homeostasis, such as diabetes, and in one particular embodiment type II diabetes. Ciclopirox is shown to stimulate p21 expression by mechanisms that are likely p53-independent.