title: Metformin exposure and disseminated disease in patients with colorectal cancer.
abstract: BACKGROUND
  Preclinical evidence suggests a role for metformin in inhibiting tumour dissemination and metastasis. Previous studies have identified associations between metformin exposure and improved colorectal cancer survival. This study aimed to examine associations between metformin exposure and the odds of presenting with disseminated disease among colorectal cancer patients.
  
  
  METHODS
  Colorectal cancer patients diagnosed 2001-2006 were identified from the National Cancer Registry Ireland. A linked national pharmacy claims database was used to determine exposure to anti-diabetic medications prior to diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for associations between metformin use (versus non-metformin anti-diabetic drugs) and odds of presenting with disseminated disease (lymph node positive/metastatic). Analyses were stratified by anti-diabetic drug co-prescription and intensity of metformin exposure.
  
  
  RESULTS
  The study population included 241 metformin-exposed diabetics, 129 non-metformin-exposed diabetics, and 4277 non-diabetic patients. In multivariate analysis, odds of disseminated disease were lower in metformin-exposed diabetics, compared with non-metformin-exposed diabetics, though not statistically significant (OR=0.66, 95% CI 0.39-1.12). In analyses stratified by metformin dosing intensity and anti-diabetic drug co-prescription, the odds were further from unity and approached significance in diabetics with high intensity, exclusive metformin use (OR=0.52, 95% CI 0.25-1.10).
  
  
  CONCLUSIONS
  While overall there was no statistically significant association between metformin exposure and disseminated colorectal cancer at diagnosis, there was a suggestion that high intensity, exclusive metformin use may be associated with reduced odds of disseminated disease. The number of patients in these subgroup analyses was small, and further investigation in larger studies is warranted.
authors.affiliation: Department of Pharmacology & Therapeutics, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.
authors.forename: Susan
authors.initials: S
authors.lastname: Spillane
authors.affiliation: Department of Pharmacology & Therapeutics, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Bennett
authors.affiliation: National Cancer Registry Ireland, Building 6800, Cork Airport Business Park, Kinsale Road, Cork, Ireland.
authors.forename: Linda
authors.initials: L
authors.lastname: Sharp
authors.affiliation: Department of Pharmacology & Therapeutics, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8, Ireland. Electronic address: barront@tcd.ie.
authors.forename: Thomas I
authors.initials: TI
authors.lastname: Barron
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000473:pathology*; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007494:Ireland; D016015:Logistic Models; D008207:Lymphatic Metastasis / Q000517:prevention & control; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis / Q000517:prevention & control
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Biguanides; Colorectal neoplasms; Diabetes mellitus; Lymph nodes; Metformin; Neoplasm metastasis; Pharmacoepidemiology; Type 2