INS and Hyperglycemia: Metformin likely exerts its antitumorigenic effects through indirect mechanisms by increasing insulin sensitivity, inhibiting liver gluconeogenesis, and reducing hyperglycemia and insulin levels [21], and direct mechanisms involving activating AMP-activated protein kinase (AMPK), followed by inhibition of the mammalian target of rapamycin (mTOR) pathway [22] and the attenuation of extracellular signal-regulated kinase (ERK) signaling [23].