INS and hyperinsulinism: Nevertheless, the proposed mechanisms responsible for the anticancer effects of metformin are not only limited to the improvement of insulin sensitivity, decreased hyperinsulinism, and the inhibition of the insulin-IGF1 axis, but also other potential direct actions, such as inhibiting the AMPK/Akt/PI3K mTor pathway and enhancing CD8+ T cells, which are key players in mediating immunity to tumors, for immune-mediator anticancer effects [38].