title: Influence of metformin use on PSA values, free-to-total PSA, prostate cancer incidence and grade and overall survival in a prospective screening trial (ERSPC Aarau).
abstract: OBJECTIVE
  To analyze the effect of the oral antidiabetic drug metformin on PSA level, free-to-total PSA ratio (f/t-ratio), PCa incidence and grade as well as mortality in men participating in a population-based screening trial.
  
  
  METHODS
  Data from 4,314 men aged 55-70 years from a population-based PSA-screening trial (ERSPC Aarau) were analyzed. Information on metformin exposure was obtained by a self-administered questionnaire. Serum PSA threshold at ≥3 ng/ml triggered prostate biopsy. Data on PCa incidence and mortality were obtained through registry linkages.
  
  
  RESULTS
  Median follow-up time was 7.6 years. Mean age at baseline was 65.5 years (±SD 4.4). In all, n = 150 (3.5 %) men used metformin [metf+]. Mean baseline PSA levels were comparable between both groups ([metf+] 1.6 ng/ml ± 2.4 vs. [metf-] 1.8ug/l ± 2.2, p = 0.4) while f/t-ratio was slightly higher in metformin users ([metf+] 30.7 % ± 10.9 vs. [metf-] 27.3 % ± 10.9, p = 0.01). Overall, n = 372 (8.6 %) PCa cases were detected. Neither cumulative PCa incidence (n = 11; 7.3 % [metf+] vs. n = 361 8.7 % [metf-]; p = 0.5) nor d`Amico risk groups were significantly different between both groups. One man in each group (metf+ 0.7 % and metf- 0.02 %) died from PCa (p < 0.0001), respectively. All-cause mortality was significantly higher among met + compared to met- (adjusted OR 2.50, 95 %CI 1.59-3.82; p = 0.0001).
  
  
  CONCLUSIONS
  No significant differences in PSA levels or PCa incidence and grade were observed. The slightly higher f/t-ratio did not result in lower PCa detection rate. Metformin users were at significantly higher risk of all-cause mortality. The relatively small number of men on metformin is a main limitation of the study.
authors.affiliation: Department of Urology, Cantonal Hospital Aarau, Aarau, 5001, Switzerland, marco_randazzo1@hotmail.com.
authors.forename: Marco
authors.initials: M
authors.lastname: Randazzo
authors.forename: Josef
authors.initials: J
authors.lastname: Beatrice
authors.forename: Andreas
authors.initials: A
authors.lastname: Huber
authors.forename: Rainer
authors.initials: R
authors.lastname: Grobholz
authors.forename: Lukas
authors.initials: L
authors.lastname: Manka
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Wyler
authors.forename: Felix F
authors.initials: FF
authors.lastname: Chun
authors.forename: Franz
authors.initials: F
authors.lastname: Recker
authors.forename: Maciej
authors.initials: M
authors.lastname: Kwiatkowski
mesh_terms: D000368:Aged; D055088:Early Detection of Cancer; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D007610:Kallikreins / Q000097:blood*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D060787:Neoplasm Grading; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000401:mortality / Q000473:pathology; D011795:Surveys and Questionnaires
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen