Originally published 7/1/2022
Here’s hot-off-the-presses news regarding the protective benefit of metformin against a nasty side effect of androgen deprivation therapy (ADT).
ADT means cutting off a man’s androgens (male hormones, including testosterone) in order to stop advanced prostate cancer (PCa) in its tracks.
“Advanced” means the cancer is no longer contained in the prostate gland has not yet spread to remote sites (metastasized) beyond the local or regional pelvic area.
ADT is effective in halting the progression of PCa, but it comes with a price. It is not curative, and ADT has several unpleasant side effects. One of these is metabolic syndrome (MS) which means putting on abdominal fat and developing low blood sugar.
Now, metformin helps control metabolic syndrome among diabetics, so a multicenter team of researchers wondered if it could do the same for non-diabetic PCa patients on ADT.
Sadly, the small study showed no effect of metformin against ADT-related MS.[i] Since there were only 36 patients in the study, and they were only tracked for 28 weeks, it may be worth exploring this question in a larger, longer study.
I want to report on two fairly new published papers on prostate cancer (PCa) patients who are also diabetic. Specifically, these papers contain information that has implications for non-diabetic PCa patients, regarding ongoing pursuit of a common diabetes treatment that may actually prevent or even treat PCa.
The treatment in question is the drug metformin, now the most commonly used medication to control type 2 diabetes. As the Mayo Clinic writes, it is “generally the first medication prescribed for type 2 diabetes. It works primarily by lowering glucose production in the liver and improving your body’s sensitivity to insulin so that your body uses insulin more effectively.”
I have previously posted blogs on metformin topics such as its potential as an anti-aging drug, or how it might help prevent PCa. While evidence in favor of either outcome is exciting, there is also vague or conflicting evidence suggesting the contrary. Does metformin serve PCa patients well, or doesn’t it? More recently, I became curious about the effect of metformin on PCa patients who are already using the drug for their diabetes Again, the results are mixed. These two studies illustrate the uncertainty:
- A 2021 study out Finland assembled data on over 14,000 PCa patients who had been treated with prostatectomy.[ii] Any use of antidiabetic drugs was gathered from their prescription records, and the authors performed statistical correlations between their medications and whether they eventually had recurrence requiring androgen deprivation therapy (ADT) or died from their PCa. They found that prediagnostic use of antidiabetic drugs was not associated with PCa mortality risk; however, prediagnostic use of metformin was linked with less risk of going on ADT whereas high-dose insulin users had a greater risk of going on ADT. Also, postdiagnostic use of metformin was linked with reduce risk of death, as opposed to other antidiabetic with higher risk of PCa specific death.
- In contrast to the Finnish paper, during the same year a Canadian study concluded otherwise, this time taking gene variants into account. Lee, et al. (2021) explored links between metformin use and risk of high-grade (Grade Group ≥ 2) and overall PCa.[iii] The authors were interested in genomic variations that might have a bearing upon metformin’s interaction with metabolic pathways in diabetic PCa patients, as they gathered statistics based on 3481 patients in their database. 132 of them were taking metformin at the time of diagnosis. These patients tended to be older and non-Caucasian with higher BMI (bode mass index), Gleason score, and number of positive cores. The researchers found that metformin use was associated with higher risk for high-grade PCa and overall PCa. Only two genomic variants had “significant interaction” with metformin to account for these findings, suggesting the need for further study.
What are we to make of such conflicting findings? Ahn, et al. (2020) articulate the dilemma well:
Research has shown that PCa development and progression are associated with metabolic syndrome and its components. Therefore, reduction in the risk of PCa and improvement in survival in metformin users may be the results of the direct anti-cancer mechanisms of the drug or the secondary effects from improvement of metabolic syndrome. In contrast, some research has suggested that there is no association between metformin use and PCa incidence or survival.[iv]
Perhaps this ambiguity of does-it-or-doesn’t-it only us to a place of surrender into not knowing, for now. Throughout history, many luminaries in the sciences have vigorously, determinedly sought understanding, only to have to come to terms with mystery that presents no immediate solution. I like a quote from a 2019 article in Scientific American. The author, Sara Gottlieb-Cohen, writes,
Scientists are experts at embracing the unknown. It can embrace a sense of wonder but also of disorientation. Acknowledging what we do not know does not always feel good, but it pushes us to seek a deeper understanding of the world around us.[v]
At the Sperling Prostate Center, we continually seek a deeper understanding of prostate cancer—how to understand, detect, diagnose and treat it in ways that serve our patients’ best interests. It’s truly a treasure hunt, and we optimistically anticipate the reward of soon discovering whether metformin lives up to the many hopes that it can help PCa patients whether they are diabetic or not.
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] Mahalingam D, Hanni S, Serritella AV, Fountzilas C et al. Utilizing metformin to prevent metabolic syndrome due to androgen deprivation therapy (ADT): a randomized phase II study of metformin in non-diabetic men initiating ADT for advanced prostate cancer. Oncotarget. 2023 Jun 19;14:622-636.
[ii] Joentausta RM, Rannikko A, Murtola TJ. Prostate Cancer-specific Survival After Radical Prostatectomy Is Improved Among Metformin Users but Not Among Other Antidiabetic Drug Users. Eur Urol Open Sci. 2021 Nov 17;34:86-93. iii Lee MJ, Jayalath VH, Xu W, Lu L, Freedland SJ, Fleshner NE, Kulkarni GS, Finelli A, van der Kwast TH, Hamilton RJ. Association between metformin medication, genetic variation and prostate cancer risk. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):96-105.
[iii] Lee MJ, Jayalath VH, Xu W, Lu L, Freedland SJ, Fleshner NE, Kulkarni GS, Finelli A, van der Kwast TH, Hamilton RJ. Association between metformin medication, genetic variation and prostate cancer risk. Prostate Cancer Prostatic Dis. 2021 Mar;24(1):96-105.
[iv] Ahn HK, Lee YH, Koo KC. Current Status and Application of Metformin for Prostate Cancer: A Comprehensive Review. Int J Mol Sci. 2020;21(22):8540. Published 2020 Nov 12. doi:10.3390/ijms21228540 v Gottlieb-Cohen, Sarah. “Science Means Not Knowing.” Scientific American, July 19, 2019. https://blogs.scientificamerican.com/observations/science-means-not-knowing/
[v] Gottlieb-Cohen, Sarah. “Science Means Not Knowing.” Scientific American, July 19, 2019. https://blogs.scientificamerican.com/observations/science-means-not-knowing/
About Dr. Dan Sperling
Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.
