title: Statin use as a moderator of metformin effect on risk for prostate cancer among type 2 diabetic patients.
abstract: OBJECTIVE
  Metformin and statins have shown promise for cancer prevention. This study assessed whether the effect of metformin on prostate cancer (PCa) incidence varied by statin use among type 2 diabetic patients.
  
  
  METHODS
  The study cohort consisted of 5,042 type 2 diabetic male patients seen in the Veteran Administration Health Care System who were without prior cancer and were prescribed with metformin or sulfonylurea as the exclusive hypoglycemic medication between fiscal years 1999 and 2005. Cox proportional hazards analyses were conducted to assess the differential hazard ratio (HR) of PCa due to metformin by statin use versus sulfonylurea use, where propensity scores of metformin and statin use were adjusted to account for imbalances in baseline covariates across medication groups.
  
  
  RESULTS
  Mean follow-up was 5 years, and 7.5% had a PCa diagnosis. Statin use modified the effect of metformin on PCa incidence (P < 0.0001). Metformin was associated with a significantly reduced PCa incidence among patients on statins (HR 0.69 [95% CI 0.50-0.92]; 17 cases/533 metformin users vs. 135 cases/2,404 sulfonylureas users) and an increased PCa incidence among patients not on statins (HR 2.15 [1.83-2.52]; 22 cases/175 metformin users vs. 186 cases/1,930 sulfonylureas users). The HR of PCa incidence for those taking metformin and statins versus those taking neither medication was 0.32 (0.25-0.42).
  
  
  CONCLUSIONS
  Among men with type 2 diabetes, PCa incidence among metformin users varied by their statin use. The potential beneficial influence on PCa by combination use of metformin and statin may be due to synergistic effects.
authors.affiliation: Division of Clinical Epidemiology, Department of Medicine, The University of Texas Health Science Center San Antonio, San Antonio, Texas, USA. lehman@uthscsa.edu
authors.forename: Donna M
authors.initials: DM
authors.lastname: Lehman
authors.forename: Carlos
authors.initials: C
authors.lastname: Lorenzo
authors.forename: Javier
authors.initials: J
authors.lastname: Hernandez
authors.forename: Chen-Pin
authors.initials: CP
authors.lastname: Wang
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004357:Drug Synergism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008687:Metformin