title: Metformin reduces ovarian cancer risk in Taiwanese women with type 2 diabetes mellitus.
abstract: BACKGROUND
  Whether metformin therapy affects ovarian cancer risk in Asian patients with type 2 diabetes mellitus has not been investigated.
  
  
  METHODS
  Data analysis was performed in 2014. The reimbursement databases of Taiwanese female patients with a new diagnosis of type 2 diabetes mellitus between 1998 and 2002 (n = 479,475) were retrieved from the National Health Insurance for follow-up of ovarian cancer until the end of 2009. Metformin was treated as a time-dependent variable; and of these patients, 286,106 were never-users, and 193,369 were ever-users. A time-dependent approach was used to calculate ovarian cancer incidence and estimate hazard ratios by Cox regression for never-users (as referent group), ever-users and subgroups of metformin exposure (tertiles of cumulative duration and cumulative dose).
  
  
  RESULTS
  During follow-up, 601 metformin ever-users and 2600 never-users developed ovarian cancer, representing an incidence of 49.4 and 146.4 per 100,000 person-years, respectively. The overall fully adjusted hazard ratio (95% confidence intervals) for ever-users versus never-users was 0.658 (0.593-0.730). The fully adjusted hazard ratios for the first, second and third tertiles of cumulative duration of metformin therapy were 1.169 (1.019-1.341), 0.761 (0.644-0.898) and 0.276 (0.225-0.340), respectively (p trend < 0.01) and 1.220 (1.067-1.395), 0.610 (0.513-0.725) and 0.305 (0.248-0.374), respectively (p trend < 0.01), for a cumulative dose of metformin. In additional analyses, sulfonylureas but not the other antidiabetic drugs were associated with a reduced risk of ovarian cancer.
  
  
  CONCLUSIONS
  Metformin use is associated with a decreased risk of ovarian cancer.
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, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Chin-Hsiao
authors.initials: CH
authors.lastname: Tseng
mesh_terms: D000328:Adult; D000368:Aged; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000453:epidemiology / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions; D057286:Electronic Health Records; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015994:Incidence; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D016016:Proportional Hazards Models; D012307:Risk Factors; D013222:State Medicine; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000627:therapeutic use; D013624:Taiwan / Q000453:epidemiology
chemical_list: D016588:Anticarcinogenic Agents; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: Taiwan; diabetes; epidemiology; metformin; ovarian cancer