Prostate Cancer Risk Lowered by Diabetes Drug
Originally published 7/21/2016
A certain amount of skepticism is always warranted when an unrelated drug appears to prevent prostate cancer (PCa). In this case, the diabetes drug metformin has been reported to lower PCa risk or even prevent PCa among diabetic men who take it, as the original blog below describes.
Eight years after publishing the blog, researchers from China challenged that claim in a published paper, “Does metformin really reduce prostate cancer risk: an up-to-date comprehensive genome-wide analysis.”[i]
They conducted a thorough molecular analysis of the effectiveness of metformin against 32 gene variants known to be involved in the development of prostate cancer. With one small exception, the effects were negative.
The authors concluded that their research did not support a protective role against PCa. On the other hand, a South Korean study published the same year involved a demographic analysis of over 560,000 men who were either pre-diabetic, new-onset diabetic, or longer-term diabetic.[ii]
Not only did the authors calculate any link between metabolic syndrome and PCa, they also calculated the incidence of PCa among anti-diabetic drug use, particularly metformin. Based on this data, the researchers found diabetes patients generally had lower rates of PCa regardless of whether they had metabolic syndrome.
Also, “Regarding associations of anti-diabetic drugs with the incidence of PC, DM patients who were taking less than three drugs of oral hypoglycemic agents including metformin showed a reduced risk of PC compared to patients without using metformin.”
Therefore, although the Chinese lab research found no biochemical link between metformin and PCa gene variants, the South Korean study continues to confirm population-based observations that metformin use reduces PCa risk.
The history of medicine is full of instances in which a drug fails in its intended use but ends up being triumphant with something completely unrelated. The diabetes drug metformin is the product of such a tale. Its history begins with in the 1920s with the search for a medicine to control malaria, which connects in 1949 to a “near-miraculous” cure for a particular strain of brain flu. The infectious disease specialist who used that compound called it flumamine, noting that it had the “unusual” property of lowering blood sugar. In 1957, Jean Sterne, a French physician who specialized in diabetes, read about flumamine, and tested it on animals with positive results but no toxicity. News of flumamine quickly gained attention. In 1962, a report of successful flumamine use with diabetic patients was published, and the substance was named metformin. Metformin soon became the preferred alternative to insulin, because it did not have the same potential to induce coma. Today, metformin is “the most widely used drug to treat diabetes Type 2, and is one of only two oral antidiabetic drugs on the World Health Organization (WHO) list of essential medicines.”[iii]
It would not be an exaggeration to say that metformin is something of a wonder drug. In addition to holding a victorious place over diabetes, it may also have a role to play in prostate cancer. In the May 2016 publication of a literature review and analysis by Sayyid and Fleshner, the authors suggest that metformin can be of value in preventing prostate and other cancers.[iv] They identified 21 relevant articles published from 2010-2016. They, like other authors before them, found evidence that metformin has potential value in controlling prostate cancer.
According to Sayyid & Fleshner, laboratory studies have demonstrated that metformin disrupts androgen receptor functions in prostate cancer cells, thereby discouraging proliferation. It also negatively influences how cancer cells utilize glucose (sugar), something that cancer cells need for their survival and progression. There are other biochemical interactions as well, all of which point to metformin’s ability to prevent the action of prostate cancer at the physiological level.
Several human studies have shown that metformin is associated with a lower risk of developing prostate cancer. This association is stronger the longer a patient has been on metformin. In addition, it appears that patients who are on statin drugs (to control cholesterol) in addition to metformin have an even lower risk of prostate cancer. On the other hand, there are also studies in which no correlation between metformin and prostate cancer diagnosis was apparent, so the connection remains inconclusive.
Sayyid & Fleshner note that for patients on metformin who receive prostate cancer treatment, the drug may somehow boost the effectiveness of the treatment. The authors cite evidence of lower rates of recurrence, better response to radiation therapy, and reduced likelihood of metastatic disease. As for a combined effect when metformin and statins are taken together, patients with advanced prostate cancer seem to do better when they concurrently use the two drugs.
Despite the studies that fail to show a positive action of metformin in preventing or curbing prostate cancer, Sayyid & Fleshner’s paper supports the view that there is sufficient evidence to warrant optimism over the ways in which metformin may influence prostate cancer outcomes. While more research is needed, it is exciting to think that metformin may yet prove to have value and versatility to help cancer patients as well as diabetics.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
References
[i] Zhang X, Li Z. Does metformin really reduce prostate cancer risk: an up-to-date comprehensive genome-wide analysis. Diabetol Metab Syndr. 2024 Jul 12;16(1):159.
[ii] Lee GJ, Han K, Lee SS. New findings on the effects of diabetes and anti-diabetic drugs on prostate cancer. Am J Cancer Res. 2024 Nov 15;14(11):5446-5455.
[iii] Dronsfield A, Ellis P. “Drug discovery: metformin and the control of diabetes.” Education in Chemistry. 2011 Nov;185-87. http://www.rsc.org/images/eic_nov2011_metformin_tcm18-210010.pdf
[iv] Sayyid R, Flesher N. “Potential role for metformin in urologic oncology.” Investig Clin Urol. 2016 May; 57(3): 157–164.
