Metformin can also act through direct mechanisms, i.e., by inhibiting the mTORCq pathway, but also affecting the intracellular folate levels, c-MYC activation, gluconeogenesis, liver glucose secretion and also NFkB, enhancing the p53 phosphorylation and AMPK-independent effects with the increase of mTORC1, autophagy and apoptosis of cancer cells and the reduction of ROS and cyclin D1 [88,89]. The gene discussed is NFKB1; the disease is cancer.