Metformin Linked to Longer Prostate Cancer Survival in Diabetic Men

Twenty-five percent decreased risk for cancer-related deaths seen

Cumulative exposure to metformin after prostate cancer diagnosis was linked to a nearly 25% decreased risk for cancer-related mortality in men with diabetes, according to a recent retrospective cohort study. The findings were reported in the Journal of Clinical Oncology.

“We believe this study has several implications,” said lead author David Margel, MD, PhD, a uro-oncologist at Rabin Medical Center in Petah Tikva, Israel, who conducted the research while at the University of Toronto.

“First, among diabetic men with prostate cancer, metformin should be considered the drug of choice not only for diabetes control but possibly to improve prostate cancer outcomes as well. Second, this study can serve as proof of concept for a randomized controlled trial of the use of metformin among non-diabetics to improve prostate cancer outcomes. Metformin is cheap, safe, and has minimal side effects among patients without diabetes and therefore may be an ideal drug for secondary prevention,” Dr. Margel told EndocrineWeb.

Metformin is a potent activator of AMP-activated protein kinase, an enzyme that inhibits the growth of the cancer cells, Dr. Margel said, In addition, metformin reduces insulinemia, which can drive the growth of cancer cells. “To put it very simply metformin deprives cancer cells from the energy they need for their rapid growth and proliferation,” he said.

Study Design and Findings

The study involved a cohort of 3,837 men living in Ontario, Canada, age > 66 years with incident diabetes who subsequently developed prostate cancer. Over a median follow-up of 4.64 years, 1,343 participants (35%) died and 291 (7.6%) died as a result of prostate cancer.

Cumulative duration of metformin use after prostate cancer diagnosis was associated with a significantly decreased risk of both prostate cancer-specific and all-cause mortality in a dose-dependent fashion. Every additional 6-month interval of metformin use was linked to a 24% decrease in prostate cancer-specific mortality as well as a significant decrease in all-cause mortality that declined over time. 

Commenting on the findings, Derek LeRoith MD, PhD, Director of Research, Division of Endocrinology, Diabetes and Bone Diseases, at Mount Sinai School of Medicine, in New York City, noted that metformin is not approved for use in prostate cancer and that randomized clinical trials are needed to confirm the findings. He added that the beneficial effects found as early as 6 months in a primarily white population “seems very fast” given that prostate cancer is generally not aggressive in these patients.

“On the other hand, there are multiple ongoing trials looking at metformin and its effects on breast cancer and prostate cancer, because of epidemiologic studies that suggest that use of metformin either as adjunct therapy or initial therapy may be very valuable in nondiabetics and diabetes,” he said.

“All diabetic patients should all be treated with metformin as long as there is no contraindication,” Dr. LeRoith said. “Start patients early in the disease with metformin and use as long as possible. If metformin should turn out to be beneficial for cancer, well then you hit two birds with one stone,” he noted.

Is Prostate Cancer a Metabolic Disease?

“We believe that our study adds to the growing body of evidence that prostate cancer is a metabolic disease,” Dr. Margel said. "Several studies have demonstrated that increased BMI and obesity are risk factors for prostate cancer progression, while statin use is associated with a reduced risk of advanced and fatal prostate cancer. But studies on incidence are very inconclusive. That maybe due to bias related to prostate cancer screening or alternatively may be related to the biology of the disease,” he said.

Dr. LeRoith noted that while some studies suggest that prostate cancer is less common in obese and diabetic patients, possibly owing to low testosterone and androgen levels in these patients, outcomes of prostate cancer are much worse in patients who are obese or have diabetes. “Thus, in obese patients with type 2 diabetes, it is important to detect prostate cancer as early as possible and then to determine the management for those patients because they are at increased risk for poor outcome of prostate cancer,” Dr. LeRoith said.

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