Metformin use and risk of prostate cancer: results from the REDUCE study.
The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis.
Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Tom
T
Feng
Surgery Section, Durham VA Medical Center, Durham, North Carolina. Department of Biostatistics and Bioinformatics, Duke University.
Xizi
X
Sun
Surgery Section, Durham VA Medical Center, Durham, North Carolina. Department of Biostatistics and Bioinformatics, Duke University.
Lauren E
LE
Howard
Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Adriana C
AC
Vidal
Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California.
Alexis R
AR
Gaines
Department of Urology, Mayo Clinic, Rochester, Minnesota.
Daniel M
DM
Moreira
GlaxoSmithKline Inc., R&D, King of Prussia, Pennsylvania.
Ramiro
R
Castro-Santamaria
Washington University School of Medicine in St. Louis, St. Louis, Missouri.
Gerald L
GL
Andriole
Division of Urology, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California. Surgery Section, Durham VA Medical Center, Durham, North Carolina. Stephen.Freedland@cshs.org.
Stephen J
SJ
Freedland
D000368:Aged; D001706:Biopsy; D003920:Diabetes Mellitus / Q000188:drug therapy; D004311:Double-Blind Method; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D016017:Odds Ratio; D011467:Prostate / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000517:prevention & control*; D012307:Risk Factors
D007004:Hypoglycemic Agents; D008687:Metformin; D017430:Prostate-Specific Antigen