Metformin Use Is Associated with Improved Survival in Patients with Advanced Prostate Cancer on Androgen Deprivation Therapy.

[pjoshea13]

New study below [1].

"Using national Veterans Affairs databases, we identified all men diagnosed with PCa between 2000-2008 that were treated with ADT with follow-up through May of 2016. Exclusions included treatment with ADT for ≤6 months or ADT receipt concurrently with localized radiation."

"The cohort after exclusions consisted of 87,344 patients: 61% were no DM {diabetes mellitus}, 22% were DM no metformin, and 17% were DM on metformin."

i.e. there understandably was no arm for no-DM+Metformin. Non-diabetics who use Metformin should bear in mind that the results are for diabetics.

There was "improved survival in DM on metformin (HR 0.82 ...) vs. DM no metformin (HR 1.03 ...) with no DM as referent group."

For cancer-specific survival: "improved survival in DM on metformin (HR 0.70 ...) vs. DM no metformin (HR 0.93 ...) with no DM as referent group."

"Metformin use in Veterans with PCa receiving ADT is associated with improved oncologic outcomes."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/299...

[pjoshea13]

renalandurologynews.com/pro...

"Metformin use is associated with prolonged survival among men with advanced prostate cancer receiving androgen deprivation therapy (ADT), according to a new study."

"In a study of US veterans receiving ADT for advanced PCa, Kyle A. Richards, MD, of the University of Wisconsin in Madison, and collaborators found that patients also receiving metformin for diabetes mellitus had a significant 18% decreased risk of death compared with men who did not have diabetes mellitus (reference group). In addition, metformin users had a significant 18% decreased risk of skeletal-related events (SREs) and 30% decreased risk of cancer-related death."

"“The current study is unique in evaluating the impact of metformin on ADT as these drugs may have an additive effect,” Dr Richards' team reported online ahead of print in The Journal of Urology."

[FCoffey]

I wish I could read the full article. This seems odd: cancer-specific survival (CSS) in men with diabetes but no metformin was better than in men with no diabetes!

[pjoshea13 in reply to FCoffey]

In diabetics, the ratio of no-Metformin to Metformin users was 22:17. Seems odd since I understand that it is usual to start diabetics on Metformin (it is dirt cheao & usually tolerated) & keep them on it even if Metformin by itself becomes insufficient. But a diabetic veteran would know better about such things.

Even so, many of the no-Metformin guys would presumably have used it in the past - perhaps even for a while after PCa diagnosis. Might have been good to have had a never-Metformin arm.

Diabetics get less PCa than non-diabetics. PCa is unique in that diabetics have an increased risk for all other cancers. And yet, previous research has shown diabetics with PCa to have poorer survival than non-diabetics - unless on Metformin. So as you say, the 7% reduction in cancer-specific mortality was a surprise.

Note though that overall mortality was slightly worse. Perhaps if we knew more about the competing mortality causes, things might be clearer.

How representavive of the general population were these 87,344 vets? 39% were diabetic. Isn't that high?

-Patrick

[GeorgeGlass in reply to pjoshea13]

In a study released by the BMJ, patients who underwent intensive glucose-lowering treatments increased their all-cause mortality by 19 percent, with a 43 percent increase in cardiovascular death.1

[pjoshea13 in reply to GeorgeGlass]

George,

So you have a link?

-Patrick

[pjoshea13 in reply to pjoshea13]

Got it: ncbi.nlm.nih.gov/pmc/articl...

[GeorgeGlass in reply to pjoshea13]

It looks like metformin is generally safe. It's the 2nd line diabeties drugs that cause the cardiovascular events. Black Cumin looks like a good way to treat naturally.

hopkinsmedicine.org/news/me...

easyhealthoptions.com/diabe...

livestrong.com/article/4703...

[Captain_Dave]

I have read about Metformin plus Quercetin:

Link:

ncbi.nlm.nih.gov/pubmed/296...

sciencedirect.com/science/a...

[pjoshea13 in reply to Captain_Dave]

Dave,

One could probably find synergy for Metformin & a number of other polyphenols.

There would certainly be additive benefit, with Metformin being "a potent activator of activated protein kinase (AMPK) which in turn inhibits the mammalian target of rapamycin (mTOR) and other signal transduction mechanisms" [1], & with polyphenols commonly "modulating ROS, Akt, and NF-κB pathways" [2].

But I believe there is synergy to be had in a mix of polyphenols too. While the structures are similar & there is overlap in function, they are all subtlely different. What's more: those we commonly use are not known for opposing effects.

The thing to remember though, is that for polyphenols to induce ROS (reactive oxygen species), the combined dose must be high enough that they cease to act as antioxidants.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/287...

[2] ncbi.nlm.nih.gov/pubmed/298...

[Trecento in reply to pjoshea13]

Thanks for this - and all the useful studies and reviews you post. My husband currently is taking berberine, and I have ordered the LEF metformin alternative product. The article suggests a need for further studies to determine optimal quercetin dosage: what would the combined dosage be to enable their cessation as anti-oxidants? This appears to be critical to achieving the required outcome. Perhaps I should mention that he is receiving Zolodex monthly implant, has had 2 months on Xtandi (seems to be beneficial) but his onc has now (as of 3 days back) switched this to Zytiga with Pred (no other reason but cost factor). He doesn't have prostate cancer but metastatic salivary gland cancer, which was initially treated almost 3 years back with surgery and radiation (has never had chemo).

I would hate to give quercetin at a dosage that promoted cancer cell proliferation rather than suppressed it!

[Scruffybut1]

Maybe that's why I, a type 2 diabetic on Metformin since 1990 have had excellent results from all my treatments? I remain on Metformin daily (2x850 mg tabs) despite the major disruption caused by my cancer meds throwing me at high speed into also needing insulin. Life is great. Tomorrow another day.

[PhilipSZacarias]

Hello Patrick, this adds to the growing body of work supporting the use of metformin to slow progression in PCa. I have been taking it for the last year and a half (diagnosed in Feb 2016 with mPCa) after initially taking berberine (a functional equivalent). What I don't understand is why metformin is not co-prescribed for patients starting ADT since ADT is known to promote the development of T2DM. I am going to challenge my oncologist about this during my visit with him next week. Phil

[pjoshea13 in reply to PhilipSZacarias]

Hi Philip,

Dr. Myers was distressed to find that many of his new patients were at risk for CVD. He did not consider it his job to do what a GP should have done, but felt obliged to do so.

The problem seems to be that the metabolic syndrome is not really considered to be a disease state. Pre-diabetes is not treated. etc.

And the "food pyramids" promoted by governments in the U.S. & U.K. & elsewhere are carb-heavy & fat-light resulting in meals that present a continual glucose challenge to the body.

In PCa patients, there should be zero tolerance for any degree of insulin resistance IMO. New PCa cases should be offered Metformin - perhaps regardless of insulin status - but it will take a large expensive trial before treatment protocols are affected. And who would fund such a trial?

The best hope is for PCa sites such as this one, to make patients better informed than their doctors about basic health issues that might have a bearing on PCa survival.

How many men begin ADT without a full understanding of the metabolic changes that are about to occur? These are not potential side effects but inevitable consequences. Makes perfect sense for Metformin to be recommended.

-Patrick

[PhilipSZacarias in reply to pjoshea13]

Well said and I concur that this forum is valuable because it helps fill in some of the gaps in the standard treatments we receive. Phil

[EdBar]

I am not diabetic but started using Metformin soon after my stage 4 DX over 4 years ago after reading Dr. Myers book. I became a patient of Myers back in 2015 and of course continued to take it under his direction. Dr. Sartor, Snuffy's replacement, agrees with its continued use as do my local medoncs.

So far so good along with all the other therapies I've hit my PCa with it all seems to be holding it at bay at this point. I have no plans of making any changes, if it works don't fix it.

Ed

[jdm3]

Yet another good post and supporting article that make me inclined to add Metformin. Thank you.

I am 7 months into Casodex and Lupron. 11 to go before my ADT vacation (but who’s counting?). I asked my MO (top doc at center of excellence) about Metformin and he just rolled his eyes.

I am going to show some of these recent articles to my family doc and ask if he will prescribe it for me. What is the dose of Metformin most guys on ADT usually take?

Josh

[pjoshea13 in reply to jdm3]

Josh,

The dose Dr. Myers mentions in his vlog posts is 2,000 mg / day (divided dose). This seems to be based on the Swiss study that finally convinced him:

ncbi.nlm.nih.gov/pubmed/244...

The standard pill is 500 mg. I recommend starting with one for a week or longer & gradually working up to four. I have no problem with four, but gastro issues are a potential concern. I always take with food.

Metformin is an AMPK activator & some prefer to use berberine, which is otc.

Life Extension also sells an "AMPK Metabolic Activator".

-Patrick

[PhilipSZacarias in reply to pjoshea13]

Hello Patrick, I just wanted to mention to you and to the other members of this forum who are considering taking metformin that I had to lower my dosage from 2000 mg/day to 1500 mg/day (in divided dosages) because of the antidiabetic effect of the phytochemicals that I was taking concurrently (e.g., quercetin, curcumin, resveratrol, catechins, etc). Berberine has a significant antidiabetic effect - I discontinued this phytochemical when I started taking metformin. The problem manifested itself in the morning during my daily exercise regimen (before breakfast) - I would feel out of sorts and mildly nauseated. I returned to feeling well after reducing the dosage. This effect happened twice, because I tried to raise the dosage again after several months on the reduced dosage, but could not tolerate it. I hope this is useful. Phil

[jdm3]

Thanks. I did a deep dive on Metformin on this site and Google, etc... Interesting to go back a few years and see how many studies there are that suggest a benefit. The recommended dosages are all over the place, hence my question. I have been adding some Berberine every now and then, but trying to settle on a consistent supplement protocol with Berberine/Metformin and other things.

I'm still surprised (and somewhat dismayed) that my MO dismisses Metformin so readily.

Stay well,

Josh

[GeorgeGlass]

Does anyone know it hypothesize why people taking glucose lowering meds would have an increased risk of cardiovascular related deaths? I realize that there are many treatment options, not just metformin so I wonder if metformin increases cvd deaths.

"In a study released by the BMJ, patients who underwent intensive glucose-lowering treatments increased their all-cause mortality by 19 percent, with a 43 percent increase in cardiovascular death."

[GeorgeGlass]

What do you think? Might Black Cumin have the same benefit as Metformin?

It looks like metformin is generally safe. It's the 2nd line diabeties drugs that cause the cardiovascular events. Black Cumin looks like a good way to treat naturally.

hopkinsmedicine.org/news/me...

easyhealthoptions.com/diabe...

livestrong.com/article/4703...

[SuppWife in reply to GeorgeGlass]

Very interesting!