title: Statins and Finasteride Use Differentially Modify the Impact of Metformin on Prostate Cancer Incidence in Men with Type 2 Diabetes.
abstract: BACKGROUND
  Metformin has shown promise for cancer prevention. Prior studies suggested that metformin might interact potential prostate cancer (PCa) prevention agents: finasteride and statins. This study assessed if concurrent use of statins or finasteride modified the long-term impact of metformin on PCa risk in men with type 2 diabetes (T2DM).
  
  
  METHODS
  The study cohort consisted of 71,999 men with T2DM seen in the Veteran Administration Health Care System, without prior cancer or liver diseases, nor prescription of thiazolidinediones or insulin between FY2003-FY2013. Cox proportional hazard analyses (adjusting for covariates and propensity scores of metformin use) were conducted to compare the hazard ratio (HR) of PCa associated with metformin use between statins or finasteride users and none users.
  
  
  RESULTS
  Mean follow-up was 6.4±2.8 years; 5.2% (N= 3,756) of the cohort subsequently received a PCa diagnosis. Both statins and finasteride significantly modified the impact of metformin on PCa incidence (p-value<0.001): HR's of PCa associated with metformin use were 0.89 (p-value=0.02) among non-statin/non-finasteride users, 0.73 (p-value<0.001) among statin users, and 1.42 (p-value<0.001) among finasteride users.
  
  
  CONCLUSIONS
  Metformin was associated with reduced PCa risk in men with T2DM. This impact was enhanced by statins but reversed by finasteride. Metformin, statins, and finasteride are potential PCa prevention agents. The interaction of these drugs on PCa risk needs further confirmation in other cohorts. Our finding of differential impacts of metformin, statins, and finasteride (alone or in combination) on PCa risk is informative for treatment management in men at risk for PCa and T2DM.
authors.affiliation: Department of Epidemiology and Biostatistics, University of Texas Health Science Center San Antonio, USA.
authors.forename: Wang
authors.initials: W
authors.lastname: Chen-Pin
authors.affiliation: Department of Urology, University of Texas Health Science Center San Antonio, USA.
authors.forename: Hernandez
authors.initials: H
authors.lastname: Javier
authors.affiliation: Department of Medicine; University of Texas Health Science Center San Antonio, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzo
authors.forename: John R
authors.initials: JR
authors.lastname: Downs
authors.forename: Ian M
authors.initials: IM
authors.lastname: Thompson
authors.forename: Bradley
authors.initials: B
authors.lastname: Pollock
authors.forename: Donna
authors.initials: D
authors.lastname: Lehman
keywords: Finasteride; Metformin; Prostate cancer; Statins; Type 2 diabetes