A study showing that statins used alone or in combination with metformin was associated with reduced prostate cancer mortality and all-cause mortality among men with high-risk prostate cancer may raise more questions about these already commonly used drugs.1
“Metformin is the first-line therapy for diabetic patients. The majority of diabetic patients are taking metformin and then go on to take it in combination with insulin or other drugs,” the study’s senior author, Grace Lu-Yao, PhD, MPH, told The ASCO Post. “The American Diabetes Association recommends that diabetic patients take statins because they are at risk for cardiovascular disease,” she continued. This is particularly true of older patients, such as those included in the prostate cancer study, whose median age at diagnosis was 74 years. “That is why almost all the men using metformin in our study also took statins,” she noted. Dr. Lu-Yao is Associate Director of Population Science, Sidney Kimmel Cancer Center-Jefferson Health, and Vice Chair of Medical Oncology, Sidney Kimmel Medical College, Philadelphia.
Some men may also be using metformin in an effort to reduce the risk of some cancers. Such use “is not a U.S. Food and Drug Administration–approved indication,” Dr. Lu-Yao noted, “although there is a lot in the literature in the past 10 years to suggest that either metformin or statins may be associated with lower cancer mortality.” A comprehensive review of the beneficial effects of metformin on cancer prevention and therapy was published last year in Cancer Management and Research.2
Statins for Hypercholesterolemia
“Statin use for high cholesterol is common in the general population, so many men diagnosed with prostate cancer are already taking these agents.” Dr. Lu-Yao noted.
In prostate cancer, men with high-risk disease who took atorvastatin, pravastatin, or rosuvastatin—but not lovastatin—had reduced prostate cancer mortality, compared with nonusers. This is consistent with the findings from a recent population-based cohort study using the Taiwan National Health Insurance Research Database.3 Those data showed three statins to be more effective at lowering triglycerides and low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol than other statins in patients with hypercholesterolemia.
Among the three statins cited, men who took atorvastatin had a longer median time to disease progression on androgen-deprivation therapy compared to those who weren’t treated with statins. “Although the exact mechanisms remain unknown, it is worth noting that atorvastatin exhibits a potent lipid-lowering effect per dose of any statin, one of the greatest bioavailability [measurements], and one of the longest half-lives,” the researchers wrote.
‘An Extra Boost’
The men in the recent prostate cancer study who started taking statins and metformin only after being diagnosed with prostate cancer had greater reductions in mortality risk—54% reduction in prostate cancer mortality vs a 36% reduction among all study participants using both medications. Postdiagnostic use can be considered “almost as adjuvant therapy,” Dr. Lu-Yao said. Used along with other treatments, initiating the use of statins alone or with metformin can provide “an extra boost,” she said.
“These two drugs are considered relatively safe. They do have side effects, but they are relatively mild and safe compared with other cancer therapies,” Dr. Lu-Yao added.
“Hopefully, a randomized trial could be funded to make the results more definitive, to provide a new way for patients to have different options, including treatments that are relatively safe and inexpensive for those who cannot afford a very expensive drug with a new novel therapy,” she commented.
DISCLOSURE: Dr. Lu-Yao has an immediate family member who has been employed by and has served in a leadership role for Sun Pharma Advanced Research Company and has an immediate family member who holds stock or other ownership interests in Merck.
REFERENCES
1. Tan XL, E JY, Lin Y, et al: Individual and joint effects of metformin and statins on mortality among patients with high-risk prostate cancer. Cancer Med 9:2379-2389, 2020.
2. Saraei P, Asadi I, Kakar MA, et al: The beneficial effects of metformin on cancer prevention and therapy: A comprehensive review of recent advances. Cancer Manag Res 11:3295-3313, 2019.
3. Wu SY, Fang SC, Shih HJ, et al: Mortality associated with statins in men with advanced prostate cancer treated with androgen deprivation therapy. Eur J Cancer 112:109-117, 2019.
