title: Metformin significantly reduces incident prostate cancer risk in Taiwanese men with type 2 diabetes mellitus.
abstract: BACKGROUND
  Whether metformin therapy affects incident prostate cancer risk in Asian patients with type 2 diabetes mellitus (T2DM) has not been investigated.
  
  
  METHODS
  The National Health Insurance reimbursement database of Taiwanese male patients with new-onset T2DM between 1998 and 2002 and aged ⩾40years (n=395,481) were retrieved to follow up prostate cancer incidence until the end of 2009. Metformin was treated as a time-dependent variable. Of the patients studied, 209,269 were never-users and 186,212 were ever-users. A time-dependent approach was used to calculate prostate cancer incidence and estimate hazard ratios using Cox regression for ever-users, never-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose). Sensitivity analyses were conducted in various subgroups, using time-dependent and non-time-dependent approaches.
  
  
  RESULTS
  During the follow-up, 2776 metformin ever-users and 9642 never-users developed prostate cancer, representing an incidence of 239.42 and 737.10 per 100,000 person-years, respectively. The hazard ratio (95% confidence intervals) after adjustment for propensity score (PS) for ever- versus never-users was 0.467 (0.446-0.488). The PS-adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 0.741 (0.698-0.786), 0.474 (0.441-0.508) and 0.231 (0.212-0.253), respectively (P-trend<0.001); and were 0.742 (0.700-0.786), 0.436 (0.406-0.468) and 0.228 (0.208-0.251) for the respective cumulative dose (P-trend<0.001). Sensitivity analyses consistently supported a protective effect of metformin on incident prostate cancer.
  
  
  CONCLUSIONS
  Metformin use is associated with a decreased risk of incident prostate cancer in Taiwanese male patients with T2DM.
authors.affiliation: Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Division of Environmental Health and Occupational Medicine of the National Health Research Institutes, Taipei, Taiwan. Electronic address: ccktsh@ms6.hinet.net.
authors.forename: Chin-Hsiao
authors.initials: CH
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000368:Aged; D048909:Diabetes Complications / Q000188:drug therapy* / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000150:complications* / Q000517:prevention & control; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Diabetes; Epidemiology; Metformin; Prostate cancer; Taiwan