Statin Use as a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients
Open Access
- 11 April 2012
- journal article
- Published by American Diabetes Association in Diabetes Care
- Vol. 35 (5), 1002-1007
- https://doi.org/10.2337/dc11-1829
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. 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 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.Keywords
This publication has 38 references indexed in Scilit:
- Cancer incidence in type 2 diabetes patients - first results from a feasibility study of the D2C cohortDiabetology & Metabolic Syndrome, 2011
- Body fatness and sex steroid hormone concentrations in US men: results from NHANES IIICancer Causes & Control, 2011
- Metformin in prostate cancer: two for the price of oneAnnals of Oncology, 2011
- Metabolic alterations and targeted therapies in prostate cancerThe Journal of Pathology, 2010
- AMP-activated kinase (AMPK)-generated signals in malignant melanoma cell growth and survivalBiochemical and Biophysical Research Communications, 2010
- Metformin use and prostate cancer in Caucasian men: results from a population-based case–control studyCancer Causes & Control, 2009
- New Users of Metformin Are at Low Risk of Incident CancerDiabetes Care, 2009
- Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of TherapyDiabetes Care, 2009
- Role of AMP-activated protein kinase in mechanism of metformin actionJCI Insight, 2001
- Adapting a clinical comorbidity index for use with ICD-9-CM administrative databasesJournal of Clinical Epidemiology, 1992