Struck out with metformin prescription

Three strikes and I'm out. I've now seen three doctors in the last month trying to get metforming prescribed to improve my chances of delaying or eliminating recurrence after SRT. I had recurrence from surgery after 3 years and am now 3 years out from SRT, and my numbers have gone from <.014 to .027 in the last year. I was a Gleason 4+3 with tertiary 4+4 and extracapsular extension, which puts me in medium to high risk. I'm also pre-diabetic (5.9 A1C). I showed my doctors the following article to support my case: http://www.sciencedirect.com/science/article/pii/S0302283812014728

The doctor responses were as follows, in order:
Primary care: Won't prescribe metformin because the diabetes guidelines don't call for it at with my A1C number.
Radiation Oncologist: The studies done are observational rather than controlled, so there is insufficient proof that metformin improves PC outcomes.
Nephrologist: Same story, observational studies only, and my A1C is not high enough for metformin. But when I asked him if he saw any negative effects from my taking metformin, he said he did not, but it would just be another pill to take.

I'm going back to my Primary care for one more try but I suspect the real reason, since they don't see any negatives from taking it, is fear of getting sued if something unrelated to metformin goes wrong and a lawyer finds out they prescribed it outside of guidelines.

If I can't get it anywhere else, I have the option of ordering from the gray market and taking it on my own, but I really don't want to do this. Anyone else have success in getting it prescribed?

Thanks Robert. I'm now thinking of paying out of pocket to see Snuffy Myers. I'm lucky to be just an hour away from him. if he didn't want me to take metformin I'd be happy to not take it. I'd just like it to be from someone who knows PC first hand and is a researcher.

I'm willing to bet that if metformin was a new drug, or cost thousands per pill the medical community would be all over it.

Dr. Lam has had no problem prescribing metformin and, actually, my family practice guy writes out the scripts.

It's rather ironic as metformin is one of the cheapest medications around.

Mel

If you continue to strike out, it might be worth your time to research Berberine. I'm not sure how Metformin works on PC(lowering blood insulin levels?), but if you can't get a script and are determined you need what metformin gives, Berberine appears to have many of the same effects and work in many of the same ways as Metformin:
www.ncbi.nlm.nih.gov/pubmed/18442638

Somebody said...
In study A, 36 adults with newly diagnosed type 2 diabetes mellitus were randomly assigned to treatment with berberine or metformin (0.5 g 3 times a day) in a 3-month trial. The hypoglycemic effect of berberine was similar to that of metformin. Significant decreases in hemoglobin A1c (from 9.5%+/-0.5% to 7.5%+/-0.4%, P<.01), fasting blood glucose (from 10.6+/-0.9 mmol/L to 6.9+/-0.5 mmol/L, P<.01), postprandial blood glucose (from 19.8+/-1.7 to 11.1+/-0.9 mmol/L, P<.01), and plasma triglycerides (from 1.13+/-0.13 to 0.89+/-0.03 mmol/L, P<.05) were observed in the berberine group.....................In conclusion, this pilot study indicates that berberine is a potent oral hypoglycemic agent with beneficial effects on lipid metabolism.

www.ncbi.nlm.nih.gov/pubmed/18275980

Somebody said...
This effect of berberine on prostate cancer cells was initiated by the generation of reactive oxygen species (ROS) irrespective of their androgen responsiveness.....................In conclusion, the present study reveals that the berberine-mediated cell death of human prostate cancer cells is regulated by reactive oxygen species, and therefore suggests that berberine may be considered for further studies as a promising therapeutic candidate for prostate cancer.

Post Edited (BillyBob@388) : 11/17/2015 10:03:24 AM (GMT-7)

I took metformin when my A1C got high enough and I HATED it. It was really harsh on my particular GI system. I hated it so much, I lost 35 lbs and got my A1C low enough to drop the darned stuff.

Mel, as I recall it was lots of gas-type pain and cramping. General stomach discomfort. I cut my intake by half after about a month and that helped a bit, so I knew that was the cause.

Some more information about metformin and stomach issues: it can cause acid stomach and diarrhea especially when you first start taking it and if you eat heavy carbs and greasy/fried food. So, if you cut back on bread, potatoes and rice (and anything made with sugar and flour), you will most likely avoid the gastric problems. Most patients are started on a lower dose which is increased gradually. If you are not on this for blood sugar problems, then you could certainly cut the pills in half but as always, speak to your doctor who prescribes it. Don't take this on an empty stomach because that increases your chances of a sour stomach, so take it with food.

It will not cause low blood sugar as some diabetes drugs can, so don't worry about fainting! It may cause some weight loss. People on metformin need to be monitored for kidney function because there have been cases of kidney problems in some people who have been on it for awhile. This is why you need to have lab work done a couple of times a year. Otherwise, it's been a very safe and inexpensive drug for type 2 diabetics.

Good luck with this!

Thanks for all the replies. I'm not one to take pills just to take them, and I'm aware of the diffeence between observational and controlled studies. The reason metformin has caught my interest is the several retrospective studies with significant number of cases (2901 from 1992 to 2008) that show positive results for prostate cancer, particularly in the context of radiation. Here is the one curve that really caught my eye. PC specific mortality at 10 years was 21.9% for those with diabetes who didn't take metformin vs 2.7% for diabetics who did take metformin - a huge difference. I'm not diabetic yet, so I could discount this, but the mortality for non diabetics who were not on metformin was 8.2%. So nondiabetics had an over 2X worse PC mortality rate than diabetics on metformin. I'm not a phsycian but it seems to me a no brainer that metformin did a lot of good for PC mortality even in men with diabetes, who one would think should have a higher mortality rate than non diabetics, with metformin being the difference in this observed group of men.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4034673/figure/F3/

Here is the whole study

http://www.europeanurology.com/article/S0302-2838(12)01472-8/pdf/metformin-and-prostate-cancer-reduced-development-of-castration-resistant-disease-and-prostate-cancer-mortality

It seems to me that my options are to go ahead with metformin as a one person clinical trial, or wait 15 to 20 years when I'll be in my late 80s or 90s for a controlled study. It's question of risk. Would I take metformin or any other pill to reduce weight? No, I'd rather use diet and exercise. Would I take metformin, knowing it may not work, to possibly reduce my risk of PC recurrence or mortality? As I said, it seems a no brainer.

Sheepguy said, "Guys like Myers pretty much try anything and everything and draw non scientific conclusions from the results."

Believe it or not, Myers isn't some mad scientist out there mixing his brew and experimenting on his patients with anything and everything. As far as supplements and prescriptions, he only has a handful that he generally recommends, many just to counteract the effects of hormone therapy.

Thanks Allen, for those great links. That's precisely the type of info I like to have -- the positive results as well as the negative, then I can make a more informed decision.

I need to go through those with care, but I note just browsing through that the negative reports mainly involve the question of whether metformin lowers PC risk overall, or progression after surgery. The article I quoted from in the OP involved men who had radiation, though it's not clear if radiation was a primary treatment or salvage. It's possible, and I've read as much, that metformin sensitizes cells to radiation, which may provide a benefit while undergoing treatment. If so, I've missed that boat.

Your small Swiss prospective trial has interesting results. Although, as you note, progression-free results were not impressive, I do note that "In 23 patients (52.3%) we observed a prolongation of PSA DT after starting metformin." Prolongation of PSADT is as good as progression free in many cases, depending on age. I'm 70, my PSADT has ranged from 9 to 12 months, and I figure that at a constant rate I'm good for around 15 doublings before I encounter widespread metastasis. At my current PSADT that's 10-15 years, maybe more with ADT and other treatments. But if the PSADT slowed to 2 years, I'm pretty sure something else would get me before PC. I realize PSADT isn't constant, there's plenty of other variables, etc, but this I have to work with the data I have for my individual case, and I want to have something better than a doctor telling me it's "another pill to take" as a reason to not take metformin.

Thanks again for those links!

Allen, I haven't read that particular JH paper but I can understand the difficulty of using a measure that is essentially a derivative as a surrogate end point. Nonetheless, everything I've read indicated that PSADT is one of the most valuable predictors of good outcomes after BCR. Here is a review paper. http://www.cureus.com/articles/2682-prognostic-factors-for-prostate-cancer-endpoints-following-biochemical-failure-a-review-of-the-literature

Granted, that Swiss trial had small numbers, and a lessening of PSADT in 53% of patients may not have much statistical power given the inherent variance for PSADT. It's still intriguing though.

PS I've not done HT even through my radiation for the reason you stated. I didn't want to give the cancer cells a head start in figuring out how to live without testosterone

Post Edited (reachout) : 11/18/2015 8:23:52 AM (GMT-7)

Yes please send me that article when you get a chance. about adjuvant HT during radiation, I'll just summarize my discussion with my RO. When I argued for HT, so it made the PC cells weaker during radiation, he countered that it might be best to keep them strong and dividing while being radiated. Interstingly, both he and my urologist said they could go either way, that there was no strong evidence for or against Adjuvant HT.

While it may appear that I'm clutching for straws, I think of it more as devils advocate arguments pro and con. I do appreciate the con side.

Allen - now you are worrying me with this statement: is the treatment that is thought to control the cancer actually making it harder to control?
Is there any evidence of that? My husband is taking metformin after a rise in PSA after SRT (up to .34 from .12 two years ago - SRT was 3.5 years ago). The oncologist seemed to think that although it may not necessarily help - it would "do no harm" except that it is a constant reminder of the cancer.
I think your point is there is no solid evidence either way, but it's hard to know what to do with that (not that it is your job to tell us what to do :)). When we asked the radiologist about combining ADT with the salvage radiation, he said that didn't make sense with what they thought was gleason 6 and clean pathology. Now we are regretting not pushing that as it appears to have been gleason 7 and it may have helped. It's very confusing to know when being aggressive can hurt and when it can help. He is very young so that affects decision making.