Do you use a statin drug to control cholesterol? If so, you are among the millions of U.S. adults who take this type of drug. According to a 2017 study, “The number of adults in the general population who reported using any statin increased from 21.8 million (17.9%) in 2002-2003 to 39.2 million (27.8%) in 2012-2013, representing a 79.8% increase…”

No one doubts that this common type of drug extends longevity.

Then there’s a different class of drugs called biguanides, the most well-known one of which is metformin, which impacts the body’s sensitivity to insulin. It is now the most frequently used first-line drug against diabetes, but research finds it may serve other healthy functions as well. In an earlier blog, I discussed its numerous positive effects which include fostering longer life at the cellular level, reducing cardiovascular inflammation, and having a chemopreventive effect against cancer or its recurrence.

Here again, there is broad agreement that metformin may well add years to a person’s life.

One-two punch against prostate cancer

I have posted several blogs over the years on evidence that each of these individual drugs may help reduce the chance of developing prostate cancer (PCa), or at least aggressive disease. Then, in August 2019, I wrote about the synergistic effect that occurs when both drugs are taken together, e.g., by a person with cardiovascular disease who also has diabetes. I drew upon two fairly recent and one brand new study, all of which explore combined statin-metformin use and its effect on men with PCa. The evidence pointed to lower risk of death from PCa.

Now, a new 2020 paper by a Spanish research team examines the biochemistry of this synergy.^[i] Their biological analyses were performed on a group of 75 PCa patients. For each individual drug class, they tested a few different formulations, but the net effect on key functional endpoints and associated biochemical pathway mechanisms seemed to result in tumor inhibition and longer biochemical recurrence-free survival.

This was particularly so when the two drug classes were taken in combination. To quote the team’s technical details, “These actions were mediated through modulation of key oncogenic and metabolic signalling-pathways (i.e., AR/mTOR/AMPK/AKT/ERK) and molecular mediators (MKI67/cMYC/androgen-receptor/cell-cycle inhibitors).” In other words, the drugs deliver a one-two punch to the way tumors survive and progress within their own biochemistry, or by appropriating the body’s normal biochemistry.

It was harder for tumor cells to proliferate. The effectiveness of the drug combination showed up in lower Gleason scores (diminished PCa aggression), and deterrence in rising PSA (biochemical recurrence). The authors concluded that, “…given the demonstrated clinical safety of biguanides [metformin] and statins, our results suggest a potential therapeutic role of these compounds, especially their combination, for the treatment of PCa.”

In addition to my 2019 blog, I find this study exciting as the biochemistry becomes clearer. I am optimistic that ongoing and future research will point to an optimum combination of statins and metformin that can be employed to help defeat PCa in newly diagnosed patients. The early signs point to a survival advantage for PCa patients with metastatic disease who are on statins, though they are less rosy for metformin’s impact on PCa metastasis (no advantage, may even promote progression in advanced castration-resistant PCa).

Obviously, more research is needed, but I will continue to monitor how statins and metformin combined may help patients with localized, low-to-intermediate risk disease. It’s worth asking, if these two drugs types together can deliver a blow to microscopic tumor cells, would it be a productive support strategy for focal therapy? Time will tell.

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] Jiménez-Vacas JM, Herrero-Aguayo V, Montero-Hidalgo A, Sáez-Martínez P. Clinical, cellular and molecular evidence of the additive antitumor effects of biguanides and statins in prostate cancer. J Clin Endocrinol Metab. 2020 Nov 28;dgaa877.