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Tuesday, January 5, 2016

Metformin and prostate cancer

[Updated July 6, 2019]

A 2019 review and meta-analysis by Chinese researchers based on 30 research studies reported on between 2012 and 2017 concludes that metformin improves overall survival, cancer specific survival and recurrence free survival for those with prostate cancer but does not reduce the risk of getting prostate cancer for those without prostate cancer. Patients who also had radiation had even more dramatic improvements in survival. [PMID: 30778081] [Full free text]

A 2014 article in the Journal of the National Cancer Institute by Azvolinksy [PMID: 24511112] [Full Free Text] and a 2014 article by Fleshner in the Canadian Urological Association Journal [PMID: 25243043] [Full Free Text] discuss observational studies on diabetic prostate cancer patients which have shown reduced risk of death from prostate cancer as well as reduced all cause mortality among those taking the widely used inexpensive diabetes drug, metformin. A May 2016 update by Sayyid and Fleshner [PMID: 27195314] [Full Free Text] reviews studies that show a decreased prostate cancer risk with metformin as well as beneficial effects for prostate cancer patients after treatment. Other recent work suggests benefit from combination therapy of metformin with statins [PMC3329836 full free text], [news release], p53 stabilizers [PMID: 26900800], chemotherapy [PMID: 27118574].

An undated overview by Peter Wehrwein speculates that the biological mechanism may be the lowering of insulin, lowering of blood sugar output of the liver or via interruption of signalling pathways. A number of investigations have concluded that metformin acts by blocking the glucose cancer cells need and in the absence of glucose they will turn to glutamanine and leucine. They hypothesize that interfering with glutamine and leucine might synergistically work with metformin. Note that glutamine is a non-essential amino acid (i.e. the body can produce it itself) so simply lowering the intake of glutamine-containing foods might not be effective. [PMID: 23687346] [Free full text] [PMID: 26550231] [Full free text] [PMID: 24052625] [Full free text].

Since then a 2016 paper found, in a cross sectional study of 326 cancer-free diabetic men, that metformin lowered PSA; however, in contrast other blood glucose lowering medications (sulfonylureas, thazodlidinediones) they looked at did not lower it. This suggests that other mechanisms than blood glucose lowering are responsible.  These might be  androgen receptor (AR) down-regulation, other non-AR mechanisms or reduction of inflammation or reduction of lipid levels. This study also found a dose-response effect between metformin and PSA -- those who used more than 2000 mg/day of metformin had 37% lower PSA than those who used less than 1000 mg/day. See [PMID: 27403913] [Full Free Text].

A second study, this one reporting in 2017, of 1363 diabetic cancer-free men also found that metformin users had lower PSA than non-users. [PMID: 29390570] [Full Free Text].

A 2015 meta-analysis by Wu et al found that the risk of developing prostate cancer (as opposed to the risk of death for those who have prostate cancer) is unaffected by metformin.

Confirmation of these results in diabetics and non-diabetics through randomized clinical trails is underway. See: []

A video on metformin and prostate cancer by oncologist Dr. Charles (Snuffy) Myers can be viewed here: How + When to Use Metformin.

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