title: Metformin and the risk of endometrial cancer: a population-based cohort study.
abstract: OBJECTIVE
  While some observational studies have suggested a protective effect of metformin on incident cancer, concerns about potential bias remain. We compared the incidence of endometrial cancer in metformin versus sulfonylurea initiators. Research design and methods We conducted a retrospective cohort analysis using US healthcare claims (MarketScan®), 2000-2011. We identified new users of metformin versus sulfonylureas with no prior cancer diagnoses and followed them until a diagnosis of endometrial cancer, hysterectomy, treatment change, or disenrollment. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards, using an as-treated analytic approach. Stabilized inverse probability of treatment weights were used to adjust for potential confounding at baseline.
  
  
  RESULTS
  Of 541,128 eligible women, 456,838 (84%) initiated metformin and 84,290 (16%) initiated sulfonylurea. The treatment groups differed at baseline in terms of age and recent diagnosis codes for diabetes, polycystic ovarian syndrome, and endometrial hyperplasia. Over a median follow-up of 1.2 (IQR 0.4-2.3) years and a total of 2,030,914 person-years, 729 women developed endometrial cancer. Metformin initiation was associated with a lower risk of endometrial cancer in the unadjusted analysis (HR 0.81, 95% CI 0.67-0.97). However, after balancing baseline covariates across groups, metformin was not associated with a reduced risk of endometrial cancer (HR 1.09, 95% CI 0.88-1.35). This finding was consistent across multiple sensitivity analyses and subgroup analyses in diabetic patients and relevant age groups.
  
  
  CONCLUSIONS
  In this population-based cohort of >500,000 women, initiating metformin compared with sulfonylureas was not associated with a reduced risk of developing endometrial cancer.
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States; University of North Carolina, Obstetrics and Gynecology, Division of Gynecologic Oncology, United States; University of Pennsylvania, Obstetrics and Gynecology, Division of Gynecologic Oncology, United States. Electronic address: Emily.ko@uphs.upenn.edu.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Ko
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States.
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States.
authors.forename: Jin-Liern
authors.initials: JL
authors.lastname: Hong
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States; University of Maryland, Department of Pharmaceutical Health Services Research, United States.
authors.forename: Wendy Camelo
authors.initials: WC
authors.lastname: Castillo
authors.affiliation: University of North Carolina, Obstetrics and Gynecology, Division of Gynecologic Oncology, United States.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bae-Jump
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, United States; Center for Women's Health Research, University of North Carolina, United States.
authors.forename: Michele Jonsson
authors.initials: MJ
authors.lastname: Funk
mesh_terms: D000328:Adult; D015331:Cohort Studies; D016889:Endometrial Neoplasms / Q000453:epidemiology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D015994:Incidence; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D014481:United States / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: Cohort study; Endometrial cancer risk; Epidemiology; Metformin; Sulfonylurea