Statin Use As a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients
- Donna M. Lehman, PHD1,2,3⇓,
- Carlos Lorenzo, MD1,
- Javier Hernandez, MD3,4 and
- Chen-pin Wang, PHD2,3,5
- 1Division of Clinical Epidemiology, Department of Medicine, the University of Texas Health Science Center San Antonio, San Antonio, Texas
- 2Department of Epidemiology and Biostatistics, the University of Texas Health Science Center San Antonio, San Antonio, Texas
- 3Cancer Therapy and Research Center, the University of Texas Health Science Center San Antonio, San Antonio Texas
- 4Department of Urology, the University of Texas Health Science Center San Antonio, San Antonio, Texas
- 5Veterans Evidence Based Research Dissemination and Implementation Center, San Antonio, Texas
- Corresponding author: Donna M. Lehman, .
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.
RESEARCH DESIGN AND 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 hazard 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.