title: Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.
abstract: OBJECTIVE
  Diabetic men have lowered overall prostate cancer (PCa) risk, while their risk of high-grade disease may be elevated. The antidiabetic drug metformin may reduce the risk. This study evaluated PCa incidence among users of metformin and other antidiabetic drugs in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).
  
  
  METHODS
  The study population (78,615 men) was linked to the national prescription database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for PCa were estimated using Cox regression, with medication use as a time-dependent variable. The effect of diabetes was estimated by comparing antidiabetic drug users to non-users, while drug-specific effects were evaluated within antidiabetic drug users. Analyses were performed in both study arms of FinRSPC.
  
  
  RESULTS
  Compared to non-users, men using antidiabetic drugs had lowered overall PCa risk (HR 0.85, 95% CI 0.79-0.92), and this association was not affected by PCa screening. However, the risk of metastatic PCa was increased (HR 1.44, 95% CI 1.09-1.91). Among antidiabetic drug users, metformin decreased overall PCa risk (HR 0.81, 95% CI 0.69-0.95) in a dose-dependent manner. When stratified by FinRSPC study arm, the risk reduction was observed only in the screening arm. Sulphonylureas increased the risk of metastatic PCa (HR 2.04, 95% CI 1.11-3.77). Use of thiazoledenediones or insulin was not associated with PCa risk.
  
  
  CONCLUSIONS
  Among antidiabetic drug users, metformin lowered the overall PCa risk, while the risk of metastatic disease was elevated in sulphonylurea users. As sulphonylureas stimulate insulin secretion, the results suggest that hyperinsulinemia may be a risk factor for PCa.
authors.affiliation: a School of Medicine , University of Tampere , Tampere , Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Haring
authors.affiliation: a School of Medicine , University of Tampere , Tampere , Finland.|b Department of Urology , Tampere University Hospital , Tampere , Finland.
authors.forename: Teemu J
authors.initials: TJ
authors.lastname: Murtola
authors.affiliation: c The Finnish Cancer Registry , Helsinki , Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Talala
authors.affiliation: d Department of Urology , University of Helsinki and Helsinki University Hospital , Helsinki , Finland.
authors.forename: Kimmo
authors.initials: K
authors.lastname: Taari
authors.affiliation: a School of Medicine , University of Tampere , Tampere , Finland.|b Department of Urology , Tampere University Hospital , Tampere , Finland.
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: e School of Health Sciences , University of Tampere , Tampere , Finland.
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
mesh_terms: D000368:Aged; D003920:Diabetes Mellitus / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D055088:Early Detection of Cancer; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000473:pathology; D065840:Protective Factors; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin
keywords: Cohort; diabetes mellitus; metformin; prostate cancer; risk