title: The use of metformin and the incidence of lung cancer in patients with type 2 diabetes.
abstract: OBJECTIVE
  Observational studies have associated metformin use with a decreased risk of lung cancer incidence in patients with type 2 diabetes, but the studies had important methodological shortcomings. The objective of this study was to determine whether metformin use is associated with a decreased risk of lung cancer in patients with type 2 diabetes, while avoiding previous biases.
  
  
  METHODS
  Using the U.K. General Practice Research Database, we assembled a cohort of patients newly treated with oral hypoglycemic agents (OHAs) between 1988 and 2009. A nested case-control analysis was conducted, where case subjects with lung cancer occurring during follow-up were matched with up to 10 control subjects for age, sex, calendar time, and duration of follow-up. Conditional logistic regression was used to estimate adjusted rate ratios of lung cancer associated with ever use of metformin, along with measures of duration and cumulative dose. Models were adjusted for potential confounders, which included smoking.
  
  
  RESULTS
  The cohort included 115,923 new users of OHAs, with 1,061 patients diagnosed with lung cancer during follow-up (rate 2.0/1,000 person-years). Metformin use was not associated with a decreased rate of lung cancer (rate ratio 0.94 [95% CI 0.76-1.17]). No dose-response was observed by number of prescriptions received, cumulative duration of use, and dose.
  
  
  CONCLUSIONS
  Metformin use is not associated with a decreased risk of lung cancer in patients with type 2 diabetes. The decreased risk reported in other observational studies is likely due to bias from methodological shortcomings. Nonetheless, greater consideration should be given to clarify inconsistencies between experimental models and population studies.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Brielan B
authors.initials: BB
authors.lastname: Smiechowski
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.forename: Michael N
authors.initials: MN
authors.lastname: Pollak
authors.forename: Samy
authors.initials: S
authors.lastname: Suissa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016015:Logistic Models; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000453:epidemiology*; D008297:Male; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin