Are there any material contraindications or reasons for prostate cancer patients not to take Metformin.
Other than a few specific people getting idiosyncratic gastro intestinal upset, is there any material reason most of us should not be taking metformin?
it's not "a few specific people getting idiosyncratic gastro intestinal upset." It is very common and occurs in over half of men. Why would you make this up?
Common side effects are:Diarrhea (53%)
Nausea/vomiting (26%)
Gas (12%)
Indigestion (7%)
Stomach pain (6%)
Headache (6%)
Other side effects
Weakness
Headache
Low vitamin B12 levels
Change in taste
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. There have been many recalls from tainted metformin.
More importantly, unless you are diabetic, it has no known value, especially not for prostate cancer:
prostatecancer.news/2019/11...
"Why would you make this up?"
Because I take 4g a day and never had any problem. Nothing.
And I am susceptible to gi problems otherwise.
And I just assumed the world revolves around me. LoL
Did you test your vitamin B12 levels? I did and it was very low and I stopped metformin. I just didn't feel good on it.
I read about how bad are statins, but I personally had zero side effects from crestor.
Now I am off from all drugs exept Degarelix injections and high blood pressure medication (perindopril arginine).
Thanks for you excellent comprehensive summary and analysis.
The difference between the mainly RCT:s and case-control studies of TA:s prostate cancer news and the video posted by Timotur on one hand which I must admit - on the cusp of starting metformin use - to my chagrin appear compelling, and the observational studies on the other, is mind-blowing. The following apparently well-designed meta-analysis from 2019 of 30 observational studies (25 retrospective and 5 prospective) with over 1.6 million patients, showed a huge advantage for metformin on PCa progression. An HR ratio of 0.6 for RFS in favor of metformin!!!
How can confounding data even come close to making it to a 0.6 figure? Are PCa users of metformin on average so much better on healthy living and improved anti-pc measures? It´s hard to believe, but I suppose the RCT data indicate that it is so. Why have the authors of this big meta-analysis apparently not even looked at the RCT and case-control studies? Do they live on different planets?
ncbi.nlm.nih.gov/labs/pmc/a...
The relationship between metformin and prostate cancer (PCa) remains controversial. To clarify this association, the PubMed, Embase and Cochrane library databases were systematically searched from their inception dates to May 23, 2018, using the keywords “metformin” and “prostate cancer” to identify the related studies. The results included incidence, overall survival (OS), PCa-specific survival (CSS) and recurrence-free survival (RFS), which were measured as hazard ratios (HR) with a 95% confidence interval (95% CI) using Review Manager 5.3 software. A total of 30 cohort studies, including 1,660,795 patients were included in this study. Our study revealed that metformin treatment improves OS, CSS and RFS in PCa (HR = 0.72, 95% CI: 0.59–0.88, P = 0.001; HR = 0.78, 95% CI: 0.64–0.94, P = 0.009; and HR = 0.60, 95% CI: 0.42–0.87 P = 0.006, respectively) compared with non-metformin treatment
Meta-analysis of observational studies is a quick way to get published without the time and expense of actually doing the research. In academia, getting ones name on a paper, no matter how useless the data is, is how one gets tenure.
In the end of all observational studies is a disclaimer stating that observational studies are prone to bias and should only be used for hypothesis generation, awaiting Level 1 evidence. Unfortunately, patients usually only have access to the abstract and never read the disclaimer.
I´ll take off my hat for you on this one, TA. After resting on it, I will most probably take my recently purchased one-year supply of metformin, from a country I visited without prescription formalities, to the pharmacy for destruction. My consolation is that the total cost came to 50 dollars....BTW, learned that metformin blunts exercise effects that´s a real side effect.
I would not discard observational studies per se. Sometimes they pan out. But next time around I will more deeply think through what the confounding factors can be. There is some logic to metformin users living more healthily or getting better treatments because they´ve taken the step to use a substance like that. If there is no apparent theoretical confounder I may go for the substance, if the potential payoff is big and side effects benign. Likewise, I am taking substances with just one or two small single-arm clinical trials if the possible benefit is large. But if an RCT, or new trials, come along disproving what I hoped for, I will drop it like a hot potato.
"learned that metformin blunts exercise effects that´s a real side effect."
Yes, that's a big troubling issue, isn't it.
Observational studies are worthless for making treatment decisions. They are usually not reproducible, and do not match what is later proven by large randomized clinical trials:
ascopubs.org/doi/full/10.12...
sciencenews.org/article/can...
There are many sources of bias that cannot be corrected in observational studies, such as selection bias, information bias, detection bias, ascertainment bias, lead-time bias, survival bias, and confounding. Chief among them is selection bias. Selection bias occurs when the selected study participants are systematically different in characteristics from eligible participants who are not selected for the study. It can also occur when the selected group is different in an important outcome predictor. the results might be biased. Selection bias particularly effects many metformin studies because mostly diabetics take metformin.
It is not just because of measured and unmeasured confounders (how could anyone possibly know what all the confounders are?
OTOH, a randomized controlled trial (RCT) eliminates all the above sources of bias by randomization.
RCTs have to be large enough, well done, and, because they are so carefully watched, may not reflect the real world experience. They are limited by their exact specifications.
"Observational studies are worthless for making treatment decisions."
TA
If you think about it, that just can't be so.
One of the differentiating characteristics of Dr Myers approach, was that he took in all types conjectures and non-RCT data and ran them through a risk/reward analysis.
Then current standard of care has always, and will always be flawed and even sometimes dangerous in unexpected ways and for unexpected reasons.
We all make our decisions with today's information, much of it inherently flawed.
RCT data deserves special respect. Of course. And even more so when their results are replicated multiple times by different authors at different institutions.
But most of us see benefit in considering low risk high reward pathways to supplement RCT based SOC.
And it isn't irrational to do so.
We are fighting a war. And we don't have the luxury of waiting for perfect information.
We almost lost the US Civil while relying on a general who was overly careful not to make mistakes, General George B. McClellan and replaced him with one who took risks and won battles, General Grant.
There is nothing irrational about taking calculated risks.
That's basically what Myers did so well. And he had very few if any dissatisfied patients for it.
It's an imperfect and evolving world, and we all have to our best within the envelope of the imperfect information we have today.
The RCT data of yesterday was imperfect and incomplete. As is certainly today's.
But we rely it because it's the best we have. But that's not a proper reason avoid considering low risk high options. Some of which admittedly may turn out in the future to be not so low risk.
McClellan almost lost the Civil War, Grant decisively won it.
Just Saying
Snuffy Myers was wrong as often as he was right. There is nothing wrong with taking a guess that proves to be wrong later. We can learn from failures as much as from successes. But I hope he was a good enough scientist to change his opinion when the proof arrived.
You don't speak for others- please avoid phrases like "most of us" unless you have survey data to share. In this case there is plenty of better data - you just don't like it. That's called "confirmation bias."
You have admitted you don't read the links I post. Never let the facts get in the way, eh? It doesn't seem to bother you that the vast majority of what you call "evidence" is not reproducible, at best, or is contradictory? That you may be advocating harms to other patients? No one is stopping you from taking anything you want. It's your body, your life. But when you make public claims using pseudoscience, expect to be refuted.
Here's another link you probably won't read:
prostatecancer.news/2021/07...
"You don't speak for others- please avoid phrases like "most of us" "
It's just from observation of the posts. I think it's fair to say that most of the posters attempt to do this. And believe they are doing it.
That would include pretty much anyone taking supplements.
The population I am taking this from is people posting here, not the lurkers.
Just an informal eyeball. I would say of the people posting about supplements, either pro or con, >51% have or are taking some kind of supplement.
In addition, a whole lot of people here ask about non-SOP treatments. That would mean they are exploring non-SOP treatments.
It's neither here nor there if I am right on such a niggling point. But it doesn't take much surfing around this forum to confirm that the weight of the evidence, little that there is, seems to affirm my conjecture.
Don't you think?
"Snuffy Myers was wrong as often as he was right. "
That is sort of the point.
When he was wrong with his treatments, he was not taking large risks.
He never went anywhere where he was taking large risks for little rewards. Only little risks for large rewards.
My local oncologist who handled a lot of Myers patients, would never vary from SOC like Myers, but was always very impressed with his protocols in general and his implementation of them in particular.
General Grant certainly made more mistakes than General McClellan. If you own the war like Lincoln did. That's not important. What is important is winning it.
"You don't speak for others- please avoid phrases like "most of us" unless you have survey data to share. In this case there is plenty of better data - you just don't like it. That's called "confirmation bias.""
Now your speaking for moi. LOL
1. I have the utmost respect for what you say and your analysis.
2. That I challenge it from time to time, means nothing more or less. Sometimes a cigar is just a cigar.
I don't go as deep as you. I don't pretend to. Maybe a little too much ADHD. LOL
"You have admitted you don't read the links I post. Never let the facts get in the way, eh? It doesn't seem to bother you that the vast majority of what you call "evidence" is not reproducible, at best, or is contradictory?"
You are leaking over into Ad Hominem territory. My experience, and probably yours too, when you see someone doing that, they may or may not be right, but they definitely are lacking some confidence in their own argument.
"That you may be advocating harms to other patients?" I certainly would never intentionally do that.
I put a question out there. I have not yet made up my mind. It was no more or less than a question. I thought it was a straight forward almost rhetorical question.
Clearly, it is not.
And I am actively reconsidering my current use of Metformin as a result of the answers, including your answers.
Complex biological systems are..... complicated. And medicine filled with a lot of grey area. That is why patients should always get multiple second opinions, and they can all differ and be right at the same time.
It appears that there are a lot more interacting variables at play here (statins, metformin, prostate cancer, prediabetes, diabetes, exercise, diet, ADT, high-risk\low-risk) that have yet to be sorted out. It would appear to not even be close.
And, with exceptions, I doubt that I will ever be convinced that there is a black and white truthful answer to any complex condition or treatment.
You have a tendency to believe there is. Me, not so much.
But I think it's not reasonably fair of you to excoriate my good faith for asking a serious question... that it seems others were interested in as well.
That's all.
TA
This study that someone below posted, seems to trump the other studies you cited with it's specificity.
Or at least materialy counterbalances them.
And Myers semi-standard cocktail include statins (very specifically and intentionally Crestor for some reason) and Metformin.
Does it alter your opinion in any way?
Individual and joint effects of metformin and statins on mortality among patients with high‐risk prostate cancer
ncbi.nlm.nih.gov/pmc/articl...
To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high‐risk PCa.
Results
Based on 12 700 patients with high‐risk PCa, statin alone or in combination with metformin was significantly associated with reduced all‐cause mortality (Hazard Ratio [HR]: 0.89; 95% Confidence Interval [CI]: 0.83, 0.96; and HR: 0.75; 95% CI, 0.67‐0.83, respectively) and PCa mortality (HR, 0.80; 95% CI: 0.69, 0.92) and 0.64; 95% CI, d 0.51‐0.81, respectively. The effects were more pronounced in post‐diagnostic users: combination use of metformin/statins was associated with a 32% reduction in all‐cause mortality (95% CI, 0.57‐0.80), and 54% reduction in PCa mortality (95% CI, 0.30‐0.69). No significant association of metformin alone was observed with either all‐cause mortality or PCa mortality.
Conclusions
Statin use alone or in combination with metformin was associated with lower all‐cause and PCa mortality among high‐risk patients, particularly in post‐diagnostic settings; further studies are warranted.
Cancer Med. 2020 Apr; 9(7): 2379–2389.
Published online 2020 Feb 8.
doi: 10.1002/cam4.2862
What makes one study better than another is the level of evidence and the GRADE. Nothing else. An observational retrospective study (especially not a SEER database study) NEVER counterbalances a prospective randomized clinical trial.
In fact, if you had studied my article, you would have seen the Tan et al. study is already listed there at the end of the observational studies I listed.
I’m a diabetic and on Metformin for many years. It was recently suggested to me that it interferes with PSA test results and can artificially lower them. I asked my consultant about this recently and he advised me that he believes it can but it wasn’t something he was concerned about. Is this something you have information on or an opinion given your experience.
I had not heard that Metformin lowers PSA. In fact, in all the randomized trials of Metformin so far, there was no difference in PSA between the treatment and control group.
Thank you for such a quick and clear response. It helps to put my mind at ease.
"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. "
As Metformin is a prescription drug, your Doc and pharmacist should check for these, and I always ask.
"Low vitamin B12 levels"
That arguably could be a feature not a big for someone with prostate cancer.
Many on here are consuming plant-based diets and have low B12 levels. High isn't good, but low isn't good either.
True
In recent discussions on this forum Patrick says low levels of B12 and folic acid/folate ARE good when it comes to prostate cancer. But not too low, as that could effect brain and nervous system function. I trust Patrick's advice.
Trust whomever you want. I trust clinical trials.
I received xiaflex injections for Peyronies. It passed a clinical trial and was approved by the FDA. It landed me in the ER for retention and I ended up wearing a catheter for over a month. It also didn't cure the Peyronies. After more than a year dealing with Peyronies I read that Patrick's issue with Duputren's benefitted from taking Iodoral, an iodine supplement. Knowing that Xiaflex is used to treat both Duputrens and Peyronies I decided to take iodoral. In a matter of weeks my Peyronies was cured. Patrick (and supplements) 1, clinical trials zero, in my score book. Props to Patrick, so yeah he is the one I choose to trust.
Make sure your PCP knows and tests you for serum potassium, creatinine and thyroid panel.
That's solid information, I'm adding it to my info list.
I have been on Metformin since 2016. I took a B-12 dip to 390 3 years ago and doc put me on sublingual B-12 (which I now only take around 2-3 times a week) and runs around 700 currently.The first month of Metformin I worked through a few small issues (brain fog etc) by starting at a low dose. My response overall to it has been quite good.
What dose of sublingual B12 do you take?
Is it superior to B12 in pill form?
1000 mcg of Methylcobalamin B12. My doc (after Dr Myers) could keep an eye on Vit B levels (I think because of metformin). When it go close to 400 he prescribed it. I believe he felt the sublingual was better metabolized . It jumped a great deal in a short period of time. I probably only take it twice a week at this point
"More importantly, unless you are diabetic, it has no known value, especially not for prostate cancer"
Dr. Myers didn't agree with that. I frankly forget his logic. But he seemed to have a good track record of front running "standard of care" by many years.
Unfortunately, given the economics of generic drugs, we are unlikely to ever see good clinical trials on this issue.
Did you read the link? MANY clinical trials.
Snuffy Myers had that hypothesis MANY years ago.
I did now.
A very thorough article. Any here interested in Metformin should take a look at it.
prostatecancer.news/2019/11...
It does seem to me those studies pretty much suffer from confounding variables.
It is one pathway... but it seems to be a complex set of interactions.
"Snuffy Myers had that hypothesis MANY years ago."
Yes, that is sadly true
What confounding variables? It is the best evidence we have so far. The sample sizes are small though. The STAMPEDE trial in 2024 will be definitive. Until then, our best evidence is that it has no effect on prostate cancer.
This one did catch my eye:
"In a secondary analysis of two randomized clinical trial databases, there were 486 patients treated with radiation and ADT. Follow-up was over 10 years. 10-year biochemical recurrence-free survival was:
73% if they used metformin
85% if they did not use metformin
Metformin was associated with inferior biochemical outcomes"
But even here, is it that diabetics have lower survival, as opposed to the taking of Metformin.
This isn't survival, it's PSA increases.
"Many years ago" is a bit overstated. I saw him last in late 2017 and he was still a strong proponent. The "studies" were very broad in their approach; not specific to the needs of this particular group. He was a specialist and closely managed the data of his 900 patients (at the time of his retirement). Additionally, his approach was built on a multi-pathway philosophy. Among his patients, I daresay there were very few naysayers i in general (my guess). Each to his own on this issue.
If you look at the data, ALL of it came in AFTER 2017. I think he would be appalled that you are still holding him to a hypothesis he made back then without better data.
I am aware of the dates of the new studies. Thanks.
askdrmyers.wordpress.com/20...
{Is 2015 "MANY years ago?}
Here is the study that Myers found so convincing:
pubmed.ncbi.nlm.nih.gov/244...
You take 4g?
I take 4 x 500 mg = 2g.
See: straighthealthcare.com/metf... "Max: 2550 mg/day"
-Patrick
So Patrick, what is your personal take on this subject?
Are you continuing with metformin?
By the way, I think that technically the study you point out is about PSA levels, while these newer studies are about survival.
One of the problems with most Metformin studies is that the men using it are largely diabetic. The Swiss study was a 2g intervention study in non-diabetics, but they were all probably pre-diabetic at that stage.
Nothing would make me give up my 2g daily right now.
I would, however, like to see more study results, such as STAMPEDE. I was a very early user of Metformin. Before starting ADT. I'm not interested much in studies with late interventions of small numbers, etc.
There does seem to be a high preponderence of men our age with pre-diabetic syndrome, or soon to be prediabetic.
Most of us eat a western style diet that burns out our insulin generating cells early.
All of the cokes, sugar water, simple carbs we eat... put quite the load on our pancreases.
Androgen deprivation therapy certainly doesn't help.
Taking Metformin cushions that load. Why not?
The researchers conclude that drugs that reduce metabolic syndrome in diabetics do not reduce metabolic syndrome among ADT users.
ascopubs.org/doi/abs/10.120...
Wow
That is a thorough study.
Seems very very well designed.
And definitely supports your proposition, and contradicts my use of Metformin.
Unfortunately I can only access the abstract.
But it was thorough, they know it was, and in the abstract they sort of brag about it. Lol
Cursory look shows they only used 500mg metformin. To me this is a minimal dose. I had normal A1c, by restarting 2500 mg metformin in three doses. Before I had elevated psa, I using low carb and time restricted eating was able to achieve normal A1c with zero medications.
We seem to now be at the point where, instead of asking why we should take a drug, we ask why NOT take it. Wow.
Fully half the population of the US is diabetic or pre-diabetic. It is indeed a scourge of sedentary living and abysmal diet. And yes ADT exacerbates it’s effects.
However, attractive though it may seem, no amount of metformin is going to cushion anything but the illusion that changing one’s diet is optional.
"There have been many recalls from tainted metformin."
That's a recently discovered issue with many generics.
Cancer causing contaminants in low concentration because of poor quality control in India and China. Taking short cuts in processing.
Similar to the problem with heavy metal contamination in most brands of powdered protein supplements.
And the voting patterns of people our age supporting politicians who vigorously support the concept of selling political and regulatory influence to the highest bidder.
Patients and consumers never appear to be competitive bidders in that process. No lobbyists I guess.
Some online pharmacy, I forget their name, has been doing a lot of work, to test and ferret out this problem.
Probably not a good reason to avoid generics though.
"kidney function"
Funny, my nephrologist didn't see that as an issue.
I will have to talk him at my next appointment.
I would watch this and discuss with your Dr.
Conclusions: Cancer was the leading cause of mortality among adults at high risk for type 2 diabetes. Although metformin and lifestyle modification prevented diabetes, neither strategy reduced all-cause, cancer, or cardiovascular mortality rates.
youtube.com/watch?v=iByaqfm...
pubmed.ncbi.nlm.nih.gov/346...
I'm pretty darn certain that lifestyle changes delay and or prevent cardiovascular incidents and death.
Been on it for 5 1/2 years because of high blood sugar no problems ever
Lupron raised my a1c.. one whole point from prediabetes.....to igot it...wason mtfrminfor 10yrs b4 dx.....different strokes.....
Metabolic syndrome is a very common effect of ADT. Good control of insulin is a Very Good Thing. Especially if you have PCa.
Why try to think you can outsmart the scientists and Drs that have spent every day for years testing and working to find ways to help us kill or slow the beast?My friend is a well known oncologist that focuses on breast cancer. She cries at night when she loses a patient. If she could find a new treatment path, she would offer it to her patients.
I live in a more complex world than yours.
Oh but that all docs were like that.
I noticed that. You must be very very smart. In fact I am quite surprised that the mushrooms, vitamin B, pot, metformin, and other treatments that you have posted about, have not already cured your PCA. Good luck finding a cure for us simple folks.
One can always confidently fall back on Standard of Care. That works in a number of cases.
Lol
I’ve been taking 2000mg daily per Snuffy Myers originally without issue for almost 8 years. I’ve been able to maintain a normal BMI despite being on ADT since dx. None of my current MO’s, including Sartor have objected to it.
Ed
I would say there is not a definitive answer to your question. The literature is pretty balanced on both sides of the argument when you just add up papers. May be a role in suppressing metabolic effects of ADT. I would suggest you go to pubmed and put in "metformin with androgen deprivation therapy" to see how difficult it is to arrive at a definitive answer for the role of metformin in men with prostate cancer.
I found this document recently which discusses the use of statins when combined with metformin.
ncbi.nlm.nih.gov/pmc/articl...
I was prescribed metformin by my doctor to specifically treat metabolic syndrome caused by ADT. However, this prescription was provided by the same family doctor who told me not to worry about a PSA low of 5.0 and a PSA high of 7.0 over two years, so who knows. Look where it got me.
This study looks pretty compelling to me.
Individual and joint effects of metformin and statins on mortality among patients with high‐risk prostate cancer
ncbi.nlm.nih.gov/pmc/articl...
To the best of our knowledge, this is the first human study aimed to quantify the individual and joint effects of statin and metformin use among patients with high‐risk PCa.
Results
Based on 12 700 patients with high‐risk PCa, statin alone or in combination with metformin was significantly associated with reduced all‐cause mortality (Hazard Ratio [HR]: 0.89; 95% Confidence Interval [CI]: 0.83, 0.96; and HR: 0.75; 95% CI, 0.67‐0.83, respectively) and PCa mortality (HR, 0.80; 95% CI: 0.69, 0.92) and 0.64; 95% CI, d 0.51‐0.81, respectively. The effects were more pronounced in post‐diagnostic users: combination use of metformin/statins was associated with a 32% reduction in all‐cause mortality (95% CI, 0.57‐0.80), and 54% reduction in PCa mortality (95% CI, 0.30‐0.69). No significant association of metformin alone was observed with either all‐cause mortality or PCa mortality.
Conclusions
Statin use alone or in combination with metformin was associated with lower all‐cause and PCa mortality among high‐risk patients, particularly in post‐diagnostic settings; further studies are warranted.
Cancer Med. 2020 Apr; 9(7): 2379–2389.
Published online 2020 Feb 8.
doi: 10.1002/cam4.2862
Looks like metformin reduces B12 and folic acid. Isn't that, within reason, a good thing for prostate cancer? That has been the subject of very recent discussions in this community. My A1C was getting a tad high so my primary care doctor agreed to prescribe metformin just on that basis. I did communicate that I had heard that it has a beneficial effect in dealing with prostate cancer.
rscbayarea.com/integrative-....
Here's a youtube video where Dr Scholz suggests that metformin may provide a prostate cancer benefit with little risk.
Observational studies and a few trials show some improved outcomes. Many of the larger RCTs show few, if any, benefits for non-diabetics.
Very likely this is yet another drug/therapy that is context-driven. I have low body fat and high muscle mass and my a1c is good. Fasting blood glucose is fine. I have done ADT and still do short ADT periods in BAT. I cut my calories and increase my exercise. The long-term ADT results were a large fat drop and a large muscle drop to go with it. The short-term BAT ADT results are negligible on the fat front but always some muscle gain.
My context-driven take is that metformin is unlikely to help me. If I had diabetes or was on the borderline, it would probably help in many ways. But I'm not so I dumped it. Liver stress, kidney stress, GI issues, etc. are real things.
May I ask what Doc are you using for bat?
Me, my MO, and my NMD. I am trying to setup a consult with Sartor. I'll PM you the names of the docs.
I think you will find Dr. Sartor to be a good fit for you from what little I have read of your posts.
He has experience with BAT and at the time I talked to him a few years ago, he was willing to consider straight testosterone.
He came highly recommended by Dr. Myers as an intellectual equal.
He seems like a perfect fit. if I can get in to see him...
Metformin and Berberine
Metformin?
Metformin experience 
Metformin & Statins - what dosage?
