title: Metformin: risk-benefit profile with a focus on cancer.
abstract: BACKGROUND
  Epidemiological evidence suggests an increased incidence of cancer in obese, prediabetic, and diabetic patients and a reduced risk of cancer incidence and mortality in diabetic patients on metformin compared with other antidiabetic drugs. In vitro studies support the efficacy of metformin in cancer therapy and prevention. Although metformin seems to be promising as a cancer chemopreventive or therapeutic drug, the principal consideration is whether metformin will be effective in cancer clinical trials for nondiabetic subjects or only in diabetics or subjects with insulin resistance. Safety of metformin is even more important in treating nondiabetic patients.
  
  
  METHODS
  The present review focuses on epidemiological data and clinical trials testing the efficacy of metformin on cancer, the safety in nondiabetic patients and the future development of this promising drug.
  
  
  CONCLUSIONS
  Meta-analyses of epidemiological in which metformin treatment has been used for diabetic patients show a positive trend for benefit; nevertheless, clinical data outcomes are preliminary and the results of ongoing trials are awaited. The different types of cancer, heterogeneity of populations and presence of comorbidity make it difficult to determine the benefits of metformin in cancer prevention and treatment.
authors.affiliation: a 1 E.O. Ospedali Galliera, Division of Medical Oncology , Genoa, Italy andrea.decensi@galliera.it.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Provinciali
authors.affiliation: b 2 European Institute of Oncology, Division of Cancer Prevention and Genetics , Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lazzeroni
authors.affiliation: b 2 European Institute of Oncology, Division of Cancer Prevention and Genetics , Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cazzaniga
authors.affiliation: c 3 E.O. Ospedali Galliera, Division of Gynecology and Obstetrics , Genoa, Italy.|d 4 University of Genoa , Genoa, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Gorlero
authors.affiliation: e 5 National Cancer Institute, National Institutes of Health, Division of Cancer Prevention , Bethesda, MD, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Dunn
authors.affiliation: a 1 E.O. Ospedali Galliera, Division of Medical Oncology , Genoa, Italy andrea.decensi@galliera.it.|b 2 European Institute of Oncology, Division of Cancer Prevention and Genetics , Milan, Italy.|f 6 Queen Mary University of London, Wolfson Institute of Preventive Medicine , London, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
mesh_terms: D003920:Diabetes Mellitus / Q000188:drug therapy; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D015994:Incidence; D007333:Insulin Resistance; D008687:Metformin / Q000494:pharmacology*; D009369:Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications; D011236:Prediabetic State / Q000150:complications; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: clinical trials; metformin; neoplasm; safety