Current studies show that especially pancreatic, liver, endometrial, colorectal, bladder and breast cancer incidences are increased by the presence of type 2 diabetes mellitus (T2DM). Possible links between T2DM and cancer include hyperinsulinemia, dysregulation of adipocytokines and hyperglycemia as well as shared confounding risk factors. There is evidence emerging from experimental and clinical studies that metformin can play a crucial anti-cancereous role. Since 2005, multiple studies showed the association between metformin and the reduction of risk in cancers of pancreas, colorectal, stomach, liver, breast and esophagus in diabetes cases. It was also claimed to improve survival in some cancers. Metformin is an insulin sensitizer and mainly acts through inhibiting hepatic gluconeogenesis by activating LKB1/AMP-activated protein kinase (AMPK). Metformin was found to have anti-cancerous and antimetastatic effects mainly through activating AMPK dependent and independent signaling; inhibiting mTOR, MAPK, HER2, NF-κB, IGF signaling pathways and with its possible immuno-modulatory effects. Further studies are needed to evaluate the potential of metformin as adjuvant therapy for cancer especially in non-diabetic patients.
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