What could be better than searching for buried treasure for many years, then finally discovering it? The answer might be, finding buried treasure when you didn’t even know you were looking for it! In the world of prostate cancer, an unexpected treasure was discovered when a diabetes drug, metformin, appeared to have deterrent properties against prostate cancer (PCa). As I wrote in a 2017 blog:

Numerous studies have shown that metformin disrupts androgen receptor functions in prostate cancer cells, thereby keeping tumors from growing. It also interferes with how cancer cells use glucose (sugar), something that cancer cells need for their survival and progression. 

To add to that, patients who have been treated for PCa and take metformin seem to experience fewer recurrences than non-metformin patients. Again, what could be better?

Adding statin drugs to metformin increases effectiveness

Apparently, a combination of two drugs could be even better than each alone. In 2012, the journal Diabetes Care published a study titled “Statin Use as a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients.”^[iii] For an average of 5 years, the authors tracked 5042 type 2 diabetic male patients who were receiving metformin or another drug called sulfonylurea for their diabetes care through the Veteran Administration (VA). None of these men had prior cancer. Some of the men taking metformin were also taking statins for cholesterol control. During the study, 7.5% were diagnosed with prostate cancer. PCa incidence was compared between those using metformin plus statins vs. those using sulfonylurea. The authors wrote, “Statin use modified the effect of metformin on PCa incidence.” Those on statins had a significantly reduced number of PCa diagnoses while those not on statins had a significantly increased number. The authors theorized that a synergistic effect between metformin and statins occurred. That was seven years ago.

Newer studies support combination statin/metformin use against prostate cancer

Since then, more papers have appeared that affirm the results of the VA study’s findings on the use of combination statin/metformin (CSM). The following are more recent examples:

1. Lu-Yao GL et al. (2015)^[iv] – This population-based study explored the correlation between treatment with CSM and prostate cancer specific mortality (PCSM). Patients were classified according to obesity and metabolic status. (We know that obesity and diabetes frequently co-exist, leading to patients taking both classes of medication.) Using the SEER-Medicare linked databases, the authors obtained case records and medication use of 22,110 high-risk PCa patients, out of which there were 1,365 deaths due specifically to PCa (PCSM). Use of combined statin/metformin was linked with a 43% reduction in PCSM, especially in obese/diabetic patients. The authors call for further study to confirm the findings.
2. Lu-Yao GL, presentation at ASCO/GU (2018)^[v] – The presenter is also the lead author on the 2015 paper above, but it’s now three years later. The purpose of this study was to measure individual and synergistic effects of statin and metformin use in high-risk PCa patients. Again, the linked SEER/Medicare databases were queried for a total of 12,700 cases. And again, use of combined statin and metformin correlated with a sizable reduction in PCSM. Of note, this was more pronounced in obese patients, plus the statin effect varied by brand (atorvastatin had the largest reduction in PCa mortality.
3. Li K, et al. (2019)^[vi] – This most recent paper is out of Taiwan, and evaluated the use of statins and/or metformin after diagnosis in terms of PCa-specific survival. A difference between this and the two previous studies is the 567 PCa cases in the study were only patients who had high cholesterol (hyperlipidemia) and who had been treated with radiation therapy. The researchers broke the cases into statin use alone, metformin use alone, and combined statin/metformin use. They found that statin use after cancer diagnosis (and treatment) was associated significantly with lower mortality risk, whereas metformin alone was linked significantly with increased mortality risk. Combined use of the two drugs conferred a higher survival rate in this population. The authors concluded, “The finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.”

What I find most interesting about these and similar studies is the decreased risk of PCa-specific death for men with compromised health (obesity, diabetes) who develop PCa—especially high-risk PCa. This subset of PCa patients would be expected to have higher mortality rates than men who are within a favorable range for weight/body-mass index, cholesterol, healthy blood sugar levels, etc. Thus, the evidence suggests that combined statin/metformin use after PCa diagnosis does not benefit everyone. Or, if it does, it is less marked in its effect on healthy patients than it is for the obese and diabetic. And yes, more research is needed to understand the synergistic drug effect and who can benefit.  

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] Tiwari R, Fleshner N. The role of metformin, statins and diet in men on active surveillance for prostate cancer. World J Urol. 2022 Jan;40(1):61-69.
[ii] Khan S, Chang SH, Hicks V, Wang M, Grubb RL 3rd, Drake BF. Improved survival with post-diagnostic metformin and statin use in a racially diverse cohort of US Veterans with advanced prostate cancer. Prostate Cancer Prostatic Dis. 2022 Apr;25(4):707-712.
[iii] Lehman D, Lorenzo C, Hernandez J, Wang C-P. Statin Use as a Moderator of Metformin Effect on Risk for Prostate Cancer Among Type 2 Diabetic Patients. Diabetes Care 2012 May; 35(5): 1002-1007.
[iv] Lu-Yao GL, Lin Y, Moore D, Graff J et al. Combination statin/metformin and prostate cancer specific mortality: A population-based study. J Clinl Oncol. 2015 33:15 suppl, 5018-2018.
[v] Lu-Yao GL, presenter. Metformin and statin together may delay prostate cancer metastasis. Paper presented at the American Society of Clinical Oncology/Genitourinary Cancers. San Francisco. 2018.
[vi] Li K, Si-Tu J, Qiu J, Lu L et al. Statin and metformin therapy in prostatecancer patients with hyperlipidemia who underwent radiotherapy: a population-based cohort study. Cancer Manag Res. 2019 Feb 4;11:1189-1197.