New study from Finland below [1].
"Only postdiagnostic metformin use was associated with reduced risks of PCa death {53% reduction} and ADT initiation compared with nonusers."
While Metformin users would be predominantly diabetic, it looks as though "nonusers" inxlude non-diabetics.
"insulin and insulin secretagogues were associated with poor survival"
Old studies have associated diabetes with a reduced risk of PCa. I'm surprised that more hasn't been written about it, since diabetice have an increased risk for every other cancer type. A curious thing about PCa is that radio-labeled glucose PET is not a useful imaging tool, for the most part - unlike for other cancer types.
Many men at risk for PCa have some degree of insulin resistance. This causes the pancreas to secrete higher levels of insulin in an effort to overcome the resistance. If the beta cells burn out and there will no longer be enough insulin to cope with glucose spikes, and a diabetes diagnosis will be likely.
It seems obvious that, while glucose is not the preferred energy source for PCa, it may increase PCa risk via the elevation of insulin levels.
The initial treatment for diabetics involves dietary advice to control glucose spikes (the high-fat Mediterranean diet will do that), and the use of Metformin to inhibit glucose production. If this is enough to keep glucose low enough to be controled by available pancreatic insulin, the diabetic will not need to take insulin.
A diabetic who takes high levels of insulin, is back where he started before the beta cells began to fail.
The PCa literature is full of references to insulin-like growth factors (IGF-I & IGF-II) - 1,593 PubMed hits for <prostate " insulin-like growth factor">, but it is clear that the entire insulin axis is implicated. IMO
A surrogate for insulin resistance is the Triglycerides:HDL-cholesterol ratio. My rule of thumb is:
1:1 is exellent
2:1 is not good
3:1 is very bad.
Alas, a 1:1 ratio requires high-normal testosterone in my case. With ADT, I slip to 2:1. It would be far worse if I were not on 2,000 mg Metformin daily, IMO.
-Patrick
[1] pubmed.ncbi.nlm.nih.gov/349...
Eur Urol Open Sci
. 2021 Nov 17;34:86-93. doi: 10.1016/j.euros.2021.10.002. eCollection 2021 Dec.
Prostate Cancer-specific Survival After Radical Prostatectomy Is Improved Among Metformin Users but Not Among Other Antidiabetic Drug Users
Roni M Joentausta 1 , Antti Rannikko 2 , Teemu J Murtola 1 3
Affiliations collapse
Affiliations
1 Tampere University, Faculty of Medicine and Health Technology, Tampere, Finland.
2 Department of Urology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
3 TAYS Cancer Center, Department of Urology, Tampere, Finland.
PMID: 34934970 PMCID: PMC8655383 DOI: 10.1016/j.euros.2021.10.002
Abstract
Background: Metformin has been linked to improved survival among diabetic prostate cancer (PCa) patients, while hyperinsulinemia and insulin usage has been related to worse prognosis.
Objective: To evaluate the association of metformin and other antidiabetic drugs with PCa death and androgen deprivation therapy (ADT).
Design setting and participants: The study cohort included 14 424 men who underwent radical prostatectomy in Finland during 1995-2013. Cases were identified, and clinical data were collected from patient files and national registries using personal identification numbers.
Intervention: Information on the use of each antidiabetic drug during 1995-2014 was collected from prescription registry of the Social Insurance Institution of Finland.
Outcome measurements and statistical analysis: The risks of PCa death and initiation of ADT were analyzed by antidiabetic drug use with the Cox regression method. Each antidiabetic drug group was analyzed separately to model simultaneous usage. Pre- and postdiagnostic uses were analyzed separately.
Results and limitations: Prediagnostic use of antidiabetic drugs in general had no association with the risk of PCa death. Prediagnostic use of metformin was related to a reduced risk of ADT initiation (hazard ratio [HR] 0.75, 95% confidence interval [CI] 0.59-0.96), while high-dose insulin users had an increased risk. Overall, antidiabetic drug use after PCa diagnosis was associated with an elevated risk of PCa death. Only postdiagnostic metformin use was associated with reduced risks of PCa death (HR 0.47, 95% CI 0.30-0.76) and ADT initiation compared with nonusers. Study limitations are missing information on glycemic control, smoking, living or exercise habits, prostate-specific antigen, and Gleason score.
Conclusions: Among surgically treated PCa patients, use of metformin was associated with improved disease-specific survival, while insulin and insulin secretagogues were associated with poor survival. Metformin might be a favorable diabetes treatment among men with PCa.
Patient summary: In this Finnish nationwide study, we found that the risks of prostate cancer death and cancer progression are lowered among metformin users, but not among other antidiabetic drug users. Metformin might be a favorable treatment choice for diabetes in men with prostate cancer.
Keywords: Androgen deprivation therapy; Cohort; Diabetes mellitus; Metformin; Prostate cancer; Radical prostatectomy; Survival.
© 2021 The Author(s).
References
Shlomai G., Neel B., LeRoith D., Gallagher E.J. Type 2 diabetes mellitus and cancer: the role of pharmacotherapy. J Clin Oncol. 2016;34:4261–4269. - PMC - PubMed
Mallik R., Chowdhury T.A. Metformin in cancer. Diabetes Res Clin Pract. 2018;143:409–419. - PubMed
Qi J., He P., Yao H., et al. Cancer risk among patients with type 2 diabetes: a real-world study in Shanghai, China. J Diabetes. 2019;11:878–883. - PubMed
Nik-Ahg F., Howard L.E., Eisenberg A.T., et al. Poorly controlled diabetes increases the risk of metastases and castration-resistant prostate cancer in men undergoing radical prostatectomy: results from the SEARCH database. Cancer. 2019;125:2861–2867. - PMC - PubMed
Murtola T.J., Sälli S.M., Talala K., Taari K., Tammela T.J., Auvinen A. Blood glucose, glucose balance, and disease-specific survival after prostate cancer diagnosis in the Finnish Randomized Study of Screening for Prostate Cancer. Prostate Cancer Prostatic Dis. 2019;22:453–460. - PubMed
Crawley D., Garmo H., Rudman S., et al. Association between type 2 diabetes, curative treatment and survival in men with intermediate- and high-risk localized prostate cancer. BJU Int. 2018;121:209–216. - PubMed
Kuo Y.J., Sung F.C., Hsieh P.F., Chang H.P., Wu K.L., Wu H.C. Metformin reduces prostate cancer risk among men with benign prostatic hyperplasia: a nationwide population-based cohort study. Cancer Med. 2019;8:2514–2523. - PMC - PubMed
Wang Y., Liu X., Yan P., et al. Effect of metformin on the risk of prostate cancer in patients with type 2 diabetes by considering different confounding factors: a meta-analysis of observational studies. Eur J Cancer Prev. 2020;29:42–52. - PubMed
He K., Hu H., Ye S., Wang H., Cui R., Yi L. The effect of metformin therapy on incidence and prognosis in prostate cancer: a systematic review and meta-analysis. Sci Rep. 2019;9:2218. - PMC - PubMed
Hitron A., Adams V., Talbert J., Steinke D. The influence of antidiabetic medications on the development and progression of prostate cancer. Cancer Epidemiol. 2012;36:e243–e250. - PubMed
Haring A., Murtola T.J., Talala K., Taari K., Tammela T.L., Auvinen A. Antidiabetic drug use and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer. Scand J Urol. 2017;51:5–12. - PubMed
Joentausta R.M., Kujala P.M., Visakorpi T., Tammela T.L., Murtola T.J. Tumor features and survival after radical prostatectomy among antidiabetic drug users. Prostate Cancer Prostatic Dis. 2016;19:367–373. - PubMed
WHO Collaborating Centre for Drug Statistics Methodology. ATC/DDD Index 2021. 10.02.2021. whocc.no/atc_ddd_index/.
Siltari A., Auvinen A., Murtola T.J. Pharmacoepidemiological evaluation in prostate cancer-common pitfalls and how to avoid them. Cancers (Basel) 2021;13:696. - PMC - PubMed
Saini N., Yang X. Metformin as an anti-cancer agent: actions and mechanisms targeting cancer stem cells. Acta Biochim Biophys Sin (Shanghai) 2018;50:133–143. - PubMed
Whitburn J., Edwards C.M., Sooriakumaran P. Metformin and prostate cancer: a new role for an old drug. Curr Urol Rep. 2017;18:46. - PMC - PubMed
Djioque S., Nwabo Kamdie A.H., Vecchio L., et al. Insulin resistance and cancer: the role of insulin and IGFs. Endocr Relat Cancer. 2013;20:R1–R17. - PubMed
Vigneri R., Goldfine I.D., Frittitta L. Insulin, insulin receptors, and cancer. J Endocrinol Invest. 2016;39:1365–1376. - PubMed