Anyone prescribe Metformin for prostate cancer not for diabetes?

[Shorehousejam]

Hi, thank you for letting my husband and I join in…

As I am trying to find information on how to deal with my husband’s sever plaque psoriasis, awful psoriasis flares after docetaxel chemotherapy infusion treatments and high glucose levels/numbers that seem to coincide with these extreme psoriasis flares rising from 140 to 260, although he is Not a diabetic, Has never been told he is a pre-diabetic or diabetic. His mother has diabetes II for most of her life.

I requested germline genetic testing, not really versed on familial and therapeutic implications with PARPi inhibitors. My husbands results show a pathogenic variant in BLM gene (heterozygous), which can be associated with the AR Bloom syndrome.

I also requested genome sequencing done on the biopsy samples

The Tumor genomics were an- Oncomine targeted panel with 

Tier 2 variants in p53 and CDH1 and Tier 3 in DNMT3A, HRAS, WT1. 

So, our next move is to send out the original 4/15 core samples to Foundation One or another group someone may recommend, I’ll start another controversial thread on that perhaps.

My husband has an active interest is his health, and he is very much in tune and in communication with his physicians. We discuss findings and coshare the results.

He discusses and decides what he wants to do and what he is comfortable doing…Livimg…

He is not interested in anything that a Physician would not suggest or recommend or prescribe.

He has been been seen by three top dermatologist at this point with no suggestion on an oral or injection form of psoriasis therapy that is not a suppressant.

Please read and digest the below with abject caution, it’s not advice as it’s just me sharing some reading material. Please take all with a pinch of salt with a grain of humor.

More Reading on Metformin:

Can metformin affect prostate?

In benign prostate hyperplasia (BPH) xenograft models, metformin inhibits testosterone and attenuates prostate weight and pathological alterations31.

These findings suggest that metformin not only reduced the side effects of ADT but also acted as chemotherapy for ADT through testosterone inhibition.

Summary

While the body of evidence to support a role for metformin in prostate cancer therapy is rapidly growing, there is still insufficient data from randomised trials, which are currently still ongoing. However, evidence so far suggests metformin could be a useful adjuvant agent, particularly in patients on ADT.

urotoday.com/conference-hig...

stampedetrial.org/media/196...

pubmed.ncbi.nlm.nih.gov/262...

clinicaltrials.gov/ct2/show...

ncbi.nlm.nih.gov/pmc/articl...

dovepress.com/statin-and-me...

The study included 567 patients. Patients who used statins or metformin after prostate cancer diagnosis had longer average survival times (9.3 years and 8.1 years, respectively; P=0.001) compared with patients who persistently used or used the medicines prior to cancer diagnosis. Multivariate Cox regression analysis found that patients treated with statins after cancer diagnosis were significantly associated with a lower risk of mortality (aHR =0.24, 95% CI =0.09–0.66) compared to patients who did not use statins during the study period. Patients treated with metformin after cancer diagnosis were significantly associated more with an increased risk of mortality (aHR =6.78, 95% CI =2.45–18.77) compared to patients who did not use metformin during the study period. Sensitivity analysis revealed that the average survival time was similar among different medicine use groups in patients with diabetes. Conclusion: The finding suggests that statins and metformin use after prostate cancer diagnosis may increase survival in patients with hyperlipidemia and radiotherapy.

Hyperglycaemia-induced resistance to Docetaxel is negated by metformin: a role for IGFBP-2

ncbi.nlm.nih.gov/pmc/articl...

ASCO 2019: TAXOMET: Docetaxel Plus Metformin Versus Docetaxel Plus Placebo in Metastatic Castration Resistant Prostate Cancer Chicago, IL (UroToday.com)

Docetaxel is a standard of care in metastatic castration-resistant prostate cancer (mCRPC), however it is still a palliative treatment with a median overall survival of ~3 years in the first line setting. Thus, innovative strategies to improve survival outcomes are needed. The rationale for using metformin as an anti-cancer drug is such that since it decreases glucose metabolism in the cell, there is an effect on the mitochondria leading to cell cycle arrest.

   There is also further rationale for combining docetaxel and metformin:Metformin decreases prostate cancer incidence in a large cohort study (OR 0.84, 95% CI 0.74-0.96)1Metformin improves time to castration-resistance and survival in prostate cancer diabetic patients compared to non-metformin users2Metformin may be an effective chemosensitizer for docetaxel in preclinical models3It is a well-known antidiabetic molecular, low cost, and with minimal side effectsAs such, the addition of metformin could enhance docetaxel efficacy in mCRPC patients. Marc Martin, MD, and his colleagues from France presented results of their trial assessing the efficacy of metformin in combination with docetaxel.

nature.com/articles/s41598-...

Association between metformin medication, genetic variation and prostate cancer risk

nature.com/articles/s41391-...

renalandurologynews.com/hom...

"Jonathan Rauch in “The Constitution of Knowledge: A Defense of Truth” describes:

No one on a patient forum is a doctor, and no one’s advice or personal experience should be taken as definitive. Anecdotes are not evidence. Check everything with your doctor. It is entirely appropriate to ask for source material for advice that goes beyond the standard-of-care, and to discuss those sources with your doctor. But remember that doctors may have little patience for sources that do not come from peer-reviewed journals or are low-level or low-quality evidence

[Tall_Allen]

So far, all the best evidence is that metformin does nothing for prostate cancer.

prostatecancer.news/2019/11...

[Shorehousejam in reply to Tall_Allen]

your article is from 2019

There are some very real concerns of the use of Metformin with certain germ lines and genomic mutations. Sited links above.

Another below is in reference to a different perspective.

In benign prostate hyperplasia (BPH) xenograft models, metformin inhibits testosterone and attenuates prostate weight and pathological alterations31.

These findings suggest that metformin not only reduced the side effects of ADT but also acted as chemotherapy for ADT through testosterone inhibition.

[Shorehousejam in reply to Shorehousejam]

The effects of metformin were:

Time to castration resistance was delayed in the high-risk group and in those with stage N1Time to castration resistance was not slowed significantly in men staged M1, especially no effect in those with a high volume of metastases.

There was no effect on PSA

There was no effect on survival

So metformin may slow progression among men who may be cured by radical therapy (removing or irradiating the prostate with or without pelvic lymph nodes) anyway. It is possible that with larger sample size and longer follow-up there may be an effect on survival among metastatic men, but the lack of a PSA response suggests that won't happen.BIMET-1 RCT28 patients with recurrent prostate cancer were given either metformin or observation for 8 weeks. All patients had a short PSA doubling time and a high body mass index. As metformin or placebo continued for 24 more weeks, bicalutamide (50 mg/day) was given to both groups.After the initial 8 weeks, PSA dropped in the metformin group

32 weeks, however, there was no difference in PSAT

trial was ended early for futility

…..

[Tall_Allen in reply to Shorehousejam]

You misunderstand how to interpret research. That can be harmful.

[Spyder54 in reply to Shorehousejam]

Thank you Shorehousejam, Re: UroToday article.

I found it interesting that a study of 1.5mm Men was not reproducable in RCT’s (Clinical Trials). It makes me curious how often that happens. Real life, vs the Lab setting.

That Metformin did have a significant effect on OS (overall survivorship). Different than other studies in last couple of years

That 17% of Metastatic Men will die of other causes, not PCa., and that 45% of those will die of Cardiovascular events. Probably not much different from the General Population of 60-80 year olds, my guess only. I thought it would be higher with us.

The Canadien Oncologists seem to be very good at communication to the General (non-Medical) population= us!

Thanks, Mike (Spyder54)

[Shorehousejam in reply to Spyder54]

Agree on that, looking for a way to bring down my husband’s high glucose levels / numbers that seem to ride along with his psoriasis flares…and finding a medication that’s not an immune suppressant to do so with…just read your bio…great information

ncbi.nlm.nih.gov/pmc/articl...

In this review, we demonstrated that metformin is safe to use in patients with psoriasis associated with diabetes, metabolic syndrome, and obesity. Antidiabetic agents may be useful for the treatment of psoriasis, especially with co-existing diabetes or when immunosuppression is contraindicated. Moreover, in psoriasis accompanied by metabolic syndrome with an inadequate response to biological therapies, metformin could be an alternative treatment and an important add-on in the management of this chronic autoimmune disease. Because comorbidities often accompany psoriasis, the therapeutic management of the disease must also take into consideration the comorbidities. There is a need to further evaluate metformin in larger clinical trials, as a therapy in psoriasis.

[Spyder54 in reply to Shorehousejam]

Harvard has a Professor that studies Human Aging. His name is Dr David Sinclair. He is convinced that Humans can live to 120, and play tennis until their last month. Part of his regimen is METFORMIN. He takes it daily. He is not diabetic. He says in a study of 40,000 People on Metformin, that there Cancer incidence was 1/8 of gen populataion (thats 87-1/2% less).

Also Dr Thomas Siefried of Boston College believes he can slow, or stop the Metastisis process (which is what actually kills us) by lowering Glucose and Glutamine. Metformin solves half of that equation, and something called DON, the other half.

Glucose is a common denominator with both guys above. You can watch some interesting Youtube vids on both above when u hv time. Mike

[Shorehousejam in reply to Spyder54]

Thank you for posting

[Tall_Allen in reply to Spyder54]

Please see comments above.

[Tall_Allen in reply to Shorehousejam]

Not all studies have equal merit. You arrived at an erroneous conclusion because you don't understand that lab studies and observational studies must not be used to drive patient decisions. Only randomized clinical studies are useful. Throw the rest in the trash.

To help you understand why, read this (the third paragraph is especially relevant):

prostatecancer.news/2019/11...

[Spyder54 in reply to Tall_Allen]

TA, you read this from URO Today above, posted by Shorehousejam?

It makes a case for Metformin, and points how the real life of 1.5 mm Canadian Men could not be replicated in RCT’s . Mike

healthunlocked.com/redirect...

[Tall_Allen in reply to Spyder54]

I've obviously seen that 2019 study he is referring to.

Remember, in the large 2019 "real world" meta-analysis study Saad is referring to (which I also mentioned in my article), the men in that study were NOT prescribed metformin for prostate cancer.

nature.com/articles/s41598-...

They were prescribed it because of other health factors (e.g., diabetes) and were seen more frequently by their doctors because of those factors. This creates ascertainment bias in their real-world study: survival improved because they were more closely watched - not because of the metformin. It also found no association with incidence of prostate cancer (no protective effect). No correction for risk factors or patient matching was possible.

All of the higher-level evidence so far is consistently showing that there is no benefit in taking metformin for prostate cancer. Also, a plausible mechanism for a beneficial effect is so far lacking.

However, all the RCTs so far have been small and short-term, so it is possible that a very large trial with long follow-up, like STAMPEDE, might yet prove there is a small effect, or metformin might prove useful if used early enough, as in men on active surveillance, or in combination with other substances (e.g., statins). There are several ongoing randomized clinical trials.

If one is overweight and pre-diabetic or at risk of metabolic syndrome, metformin makes sense.

While metformin does not have serious side effects in most men, it does have gastrointestinal side effects (diarrhea, cramps, nausea, vomiting, and flatulence). It should be avoided in men with known contraindications: lactic acidosis, metabolic acidosis, poor liver or kidney function, and hypoglycemia. There are many drug/supplement interactions that should be carefully checked.

[Spyder54 in reply to Tall_Allen]

thanks TA. Yes, I watch for updates of Arm K of the Stampede Trial (SOC + Metformin), and also Arm H ( Oligometastaic + SOC+ SABR)which is more closely my situation, also Arm L (SOC + E2). Hoping for good conclusions to all 3, IN MY LIFETIME, is the key. Cannot always wait that long. I think you must agree at some level, Mike

[Tall_Allen in reply to Spyder54]

They already published Arm H (SABR to primary):

prostatecancer.news/2018/09...

The E2 trial only published preliminary results - that it is safe and reduces T levels.

I'd be surprised if the metformin trial finds a significant effect based on several small RCTs showing no effect.

[Hidden in reply to Tall_Allen]

There is plenty of research to indicate that metformin does have a beneficial effect in suppressing prostate cancer. Here's some research that took me all of two seconds to uncover. I am sure there is a ton more if I made the effort to search further.

pubmed.ncbi.nlm.nih.gov/306...

Here's another one, on metformin's effect on BCR, buried in the link above.

pubmed.ncbi.nlm.nih.gov/262...

[EdBar]

I was prescribed Metformin by Snuffy Myers back in 2015, I’ve been taking it ever since - 2000 mg per day. I’ve been able to maintain a normal BMI, none of my current doctors including Dr. Sartor have an issue with it. As Snuffy said and I paraphrase, “it’s one of the tools in a treatment program designed to hit prostate cancer from many different angles”. I’ll continue to take it along with other treatments after all, I’m still here typing despite my G9 stage 4 dx over 8 years ago.

Ed

[Tall_Allen in reply to EdBar]

"Jonathan Rauch in “The Constitution of Knowledge: A Defense of Truth” describes knowledge as a funnel. At the top are all the guesses, the hypotheses, that drive scientific investigation. This would include (in order of increasing reliability) much of what is posted on any patient health forum every day: anecdotal “evidence” from patients; YouTube videos posted by Snuffy Myers, Mark Scholz, etc.; lab studies (mouse or test-tube); observational/epidemiological studies of patients; retrospective case-controlled studies, and systematic reviews/meta-analyses of them; cohort studies (people followed from before disease occurrence; e.g., Health Professionals Follow-Up Study, Mendelian Randomization Study). All of them are just hypothesis-generating. Most hypotheses are, and should be, wrong. Science depends on evaluating lots of hypotheses. There is no shame in guessing wrong; the only problems are when guessing stops and when one confuses a guess for a fact."

prostatecancer.news/2022/07...

[EdBar in reply to Tall_Allen]

TA, no need for you to respond to any of my posts or reply’s, thank you.

Ed

[Spyder54 in reply to Tall_Allen]

I like what TA had said here. 100%. It is fundamental in how we view this disease. Sometimes that funnel is 10 years long/deep, and many of us dont have that long to see what comes out at the tip of the funnel.

So far SOC is not Curative for Advanced PCa, so I am a huge believer in “No Stone Unturned”. I like to see everthing. I have seen SOC change at least 3x since my Dx in Oct 2020.

I like what Mark Scholz has to say in his video’s. He has a lot of patients and see’s real world results from different approaches. All of this data is what we need to make decisions.

In the end, we have to live or die with our decisions, but they are ours. What works for me doesnt necessarily work for you.

Mike

[Tall_Allen in reply to Spyder54]

What I tried to lay out is a way patients can use to evaluate evidence. There are a lot of stones to turn out there, and they are not equal. Of course, any patient is free to take his advice from a youtube video, but that is outside of way the scientific community agrees upon truth.

[Spyder54 in reply to Tall_Allen]

yes, I agree. And yes, you laid out the logic of the Scientific Community very well. As always, we appreciate you TA.

Sincerely, Mike

[Hidden in reply to EdBar]

I requested a metformin prescription from my GP after learning of the benefits of metformin on this site. I don't have diabetes but my A1C was above the healthy threshold. It has knocked A1C down. I'm not on ADT but my PSA has stabilized at 1.8. Coincidence? I received HIFU surgery six years ago. I've been lectured by TA on both of these 'mistakes'.

[EdBar]

TA It’s a request made politely and I’m not interested in your replies so please refrain thank you.

Ed

[Schwah in reply to EdBar]

EdBar, what you need to understand is that TA is not replying to just you. These are not one on one personal Messages. There are literally thousands of PC patients participating here. And most of us like to hear alternative views and arguments in order to help us to decide our own paths forward. That is literally the purpose of this site. So While we appreciate your posts we also appreciate those of others with perhaps opposing views. So please do not urge others not to reply as many of us want to hear.

Schwah.

[EdBar in reply to Schwah]

I’ve been on this site for several years now and I know how it works. TA replied to MY response to the original message that was posted, and I asked him not to reply to any of MY responses or posts. I was sharing my personal experience with the original poster and as he often does when he doesn’t agree with something he attempted to dismiss my reply. Why he feels the need to do that I don’t know. Of course he can post an alternative view, I just asked him politely not to post replies to what I post, I prefer to listen to my doctors, which he is not.

Ed

[Tall_Allen in reply to EdBar]

I appreciate your civility, but will not agree to your request. We are all posting publicly. I don't actively look for misinformation, but when I see it, I respond. If you don't want to see my response, you have the option of responding to posters privately. I do wish this site had an "ignore" button as other sites do.

[EdBacon in reply to Tall_Allen]

Agree. People who post here should not take it personally if their misinformation is challenged. As they saying goes, "everyone is entitled to their own opinion, but not their own facts"

The problem I see here is that many people take "ownership" of unproven alternatives to science-based treatments. Then they feel obligated to defend them, regardless of the science.

Everyone here is free to try whatever unproven stuff they want, just don't start preaching your religion to rest of the forum unless you are willing to be challenged.

[EdBar in reply to Tall_Allen]

I was posting my experience, so I don’t know how that is misinformation.

Ed

[Tall_Allen in reply to EdBar]

There are no qualified doctors who consider themselves to be infallible. Top doctors understand the difference between a hypothesis and a fact. Many patients do not.

[EdBar in reply to Tall_Allen]

Once again Allen, I was sharing my experience, I wasn’t giving advice to anyone. I’m not a doctor and therefore not qualified to give advice just as no one should who is not a doctor, especially when dealing with men with advanced stage disease.

So I’m not sure why you feel it’s necessary to lend your personal opinion to someone’s experience, especially when it involves a medication prescribed by a highly qualified medical oncologist who specializes in prostate cancer.

[Tall_Allen in reply to EdBar]

The best data available are not "my personal opinions" as you call it. The fact is that the best data available so far, shows no benefit. That is not a matter of opinion.

[EdBar in reply to Tall_Allen]

That’s what your thoughts are on the original post so go ahead and post your thoughts to the original post. But you replied to what I posted in a seeming attempt to dismiss it which I do not appreciate. I politely asked you not to reply to my comments or posts but you seem to have a problem with my request for some reason. So I’ll ask again that you refrain from responding to MY replies or posts, thank you.

[Gl448]

Sample of one, personal experience and anecdotal, so mostly a useless observation, but...

I've been on Metformin 500-1000mg for over a decade, it's helped with weight and metabolic syndrome blood sugar levels as measured by reduction in A1C.

However, all that metformin didn't stop me from getting Stage IIIb (at least, waiting for PET scan for better diagnosis) metastatic prostate cancer with a lesion that takes up most of one node, part of another and has spread to pelvis bone, a lymph node, the seminal vesicles, the bladder neck, the neuro/blood vessel bundles, and is spreading towards the rectum....all in less than 6 months since a PSA of 1.17 and a negative biopsy from TURP debris.

My guess is Metformin doesn't do jack squat to prevent PCa, but it's good for diabetes and weight management.

[Gl448]

Yeah. Not good. Thanks for the link.