title: Does use of metformin protect against cancer in Type 2 diabetes mellitus?
abstract: BACKGROUND
  Type 2 diabetes mellitus has been associated with an increased cancer risk, which can be modified by specific hypoglycemic drugs. In particular, metformin, the most frequently prescribed biguanide, is now considered a protective agent against cancer incidence and mortality in Type 2 diabetic patients.
  
  
  OBJECTIVE
  To review the potential associations between metformin use and cancer incidence and mortality and the possible biological links implicated in these associations.
  
  
  METHODS
  We searched English-language original investigations published through September 2011.
  
  
  RESULTS
  Metformin could block the mitogenic effects of insulin, but this effect does not entirely explain the reduction in cancer incidence. Metformin also plays a direct inhibition of cancer cell growth via the inhibitory effects of AMP-activated protein kinase on the mTOR pathway, which regulates cell growth and proliferation. Accordingly, many epidemiological studies have shown that metformin use is associated with a lower cancer incidence and mortality through a dose-response relationship, with greater exposure being associated with stronger risk reduction. Randomized clinical trials testing the effects of metformin on both recurrence and survival in early-stage breast cancer are on-going; these trials are based on pilot studies demonstrating an adjuvant effect of this drug in breast cancer.
  
  
  CONCLUSIONS
  Metformin is an inexpensive and safe drug, that may modify the increased cancer risk of Type 2 diabetic patients. On-going clinical trials will show whether this drug can enhance the effect of chemotherapy in the treatment of cancer.
authors.affiliation: Department of Internal Medicine, University of Turin, Italy. sbo@molinette.piemonte.it
authors.forename: S
authors.initials: S
authors.lastname: Bo
authors.forename: A
authors.initials: A
authors.lastname: Benso
authors.forename: M
authors.initials: M
authors.lastname: Durazzo
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D002277:Carcinoma / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D008687:Metformin / Q000494:pharmacology* / Q000627:therapeutic use*; D009369:Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin