Interestingly, as an epidemiological intervention study, the actual incidence of T2DM was followed up for about three years in thousands of subjects diagnosed with high risk of developing T2DM, and it was found that the incidence of T2DM was significantly reduced when metformin, an oral biguanide-derived antidiabetic and AMPK activator, was taken before the onset of the disease (from Diabetes Prevention Program (DPP) [143]). This evidence concerns the gene PRKAA2 and type 2 diabetes mellitus.