Effect of metformin, statin use on prostate cancer incidence may be enhanced by one another

Metformin and statins seem to have a synergistic effect on reducing prostate cancer risk, according to Donna Lehman, PhD. While metformin alone increases prostate cancer risk and statins alone decrease risk, with combined use of the two together, “we saw an even greater drop in the hazard ratio [HR] for prostate cancer” than with statins alone, she said.
     Patients with type 2 diabetes are at higher risk for high-grade prostate cancer, so methods for prevention are particularly important in this population, said Lehman, Associate Professor, Division of Clinical Epidemiology, Department of Medicine at the University of Texas Health Sciences Center in San Antonio.
     Data from 2 observational studies were consistent in finding a 20% to 40% increased risk of prostate cancer among patients with diabetes who take metformin, whereas several studies have shown a lower HR for prostate cancer among statin users.
     In the study presented here, 5042 men who responded to the Large Health Survey of Veterans and who had prescriptions for sulfonylureas or metformin as their sole class of glucose-lowering medication for at least 180 days were observed for first incidence of prostate cancer from the time of initiation of their glucose-lowering medication. Mean follow-up was 5 years.
     Subjects taking metformin only had an HR for incident prostate cancer of 2.15 compared with nonusers of metformin. A statin alone reduced risk of prostate cancer by about half. However, subjects taking both metformin and statins had a significantly reduced risk for prostate cancer, with an HR of 0.32 (68% reduction in risk) compared with those who took neither drug.
     The apparent enhanced effect of the two drug agents on prostate cancer may be related to improvement of lipid lowering with both medications compared with either alone or a combination of pleiotropic effects. For example, the combination of metformin and atorvastatin in mice seems to protect the liver in those with type 2 diabetes and hyperlipidemia; however, the combination did not improve glycemic or lipid profiles but rather improved markers of inflammatory and oxidative stress, notes Lehman.