Mechanistically, metformin’s anticancer effects may be both direct, targeting PDAC cells, and indirect, via systemic impacts on the pancreas.424 At the cellular level, activation of AMPK inhibits mTOR, ERK activation, and DNA synthesis, and concurrently inhibits YAP /TAZ to suppress PDAC development.425 Wang et al. found that metformin inhibits PDAC metastasis by inhibiting the SMAD4-HNF4G pathway.426 In addition, it exerts anti-tumor effects by lowering glucose, insulin, and IGF levels and normalizing the gut microbiota in diabetic/obese PDAC patients. This evidence concerns the gene IGF1 and neoplasm.