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Metformin and ADT

Posted 27 Dec 2019 at 12:22

I have recently had salvage RT for Biochemical Recurrence after RP and am on hormones.  I have read a quite recent and large US study


as well as many others that advocate the use of Metformin together with ADT to help with overall survival and prevention of metastases.  However doctors and specialists in the UK are unwilling to prescribe it for PCa because it requires blood sugar monitoring and they say it has not been proven yet in clinical trials that are ongoing (eg METAL and STAMPEDE).  I don't feel that I have 10 years to wait for the trials to report.  I am personally convinced by the evidence that it could be helpful and am determined to take it, but at present it seems that I will have to order it from an outside UK and non-regulated supplier because I cannot so far seem to get any GP or specialist to prescribe it (because it is not yet approved by NICE for the purpose).  I wonder if anyone else has read the evidence and has tried to get prescribed or is getting their supply from a reputable non UK source?

Posted 27 Dec 2019 at 20:47
Why don't you just ask to be referred to the Stampede trial?

I don't think it is a good idea for anyone on active cancer treatment to take unregulated drugs.

"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard

Posted 28 Dec 2019 at 12:38

I'm on metformin for this reason. I asked my onco about it (he knows I will have read the research), and he said it's a good idea. My GP was happy to prescribe it - it's cheap, and by itself, it presents negligible risk of hypo to a non-diabetic. I have measured/graphed my blood glucose regularly for years (even before PCa), because I had a relative who was diabetic, but I'm not. However, I don't think metformin would require regular blood glucose monitoring if you aren't diabetic, but I would advise everyone on hormone therapy to check their blood glucose monthly using a personal tester, because HT can push you more towards diabetes (it was significantly raising mine, but still within normal range, although the metformin seems to have stopped the raise). If you are checking your blood glucose, you might find the HT has pushed you into the range where you can ask for metformin anyway - it is a recognised side effect, and the data may help convince your onco/GP that you know what you're talking about.

One significant factor is probably that both my consultant and GP treat me as an expert patient, and allow me a lot of control over my treatment, because I took the trouble to learn a lot about it from research papers during diagnosis. This means I can have good discussions with them, and have changed the course of my diagnosis and treatment as a consequence, but with their approval.

I would encourage all patients to learn as much about their conditions as they can - it can make a significant difference to your treatment. Not all clinicians like expert patients, but fortunately, my consultant, Macmillan nurses, and GP do. I try to do my part through support groups to educate other patients. As part of this, I will be running a second session at Mount Vernon Hospital on living on hormone therapy on January 15th - PM me if you would like to attend. (It won't have anything about metformin in it though.)

Posted 29 Dec 2019 at 19:24

Thank you Andy.  I am shocked that neither my GP not the oncologists I have seen are willing to prescribe it in spite of the research papers.  My GP's are worse than useless requiring a specialist opinion. because it is outside of NICE guidelines.  My GP will not prescribe, my Oncologists will not prescribe for fear.  They are not interested in even reading the reseach - so I am stuffed.  What do i do?  I have asked the question about joining the Stampede Metformin Arm but not heard back yet (one Onco told me that I wasnt eligible).  So seems like i am heading towards having to buy it online from abroad which I dont want to do but the "system" is forcing me in that direction.  Its really unfair - what can I do?

Posted 29 Dec 2019 at 21:44
I wouldn't attach any blame to a GP for refusing to prescribe a non NICE approved substance and one that is still being trialed. Furthermore, I would say a GP was right to refer this to a Patient's Consultant. Imagine a GP prescribed a non approved substance which in due course produced a severe after effect. The GP could be in big trouble. Even a Consultant might not feel happy to prescribe this in an ad hoc way. One only has to think about the tragedy of deformed babies in the sixties found to be caused by Thalidomide to understand why NICE require vigorous testing before approving drugs/substances/treatment on the NHS as well as from a cost/benefit aspect. Unfortunately, this means that in the UK we can sometimes lag behind what has become accepted and in use in other countries. Of course anybody is free to partake of whatever they choose as long it is not illegal if they pay for it. I chose to have my first experimental radical treatment outside what the NHS would sanction.

I do hope the Metformin works well for you.

Posted 29 Dec 2019 at 21:56
I am not sure what the problem is. Just ask the onco to refer you to Stampede; the trial team are the people that will decide whether you meet the criteria. Alternatively, ask for a referral to a different onco at another hospital for a second opinion - any patient is entitled to a second opinion from another hospital.
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard

Posted 30 Dec 2019 at 02:44

Another factor for me may be that my treatment is at a research hospital, where lots of patients are on trials, so the staff are familiar, and perhaps even willing to try things that some other hospitals won't. My treatment was based on the PIVOTALboost trial, although I'm not on the trial myself.

So if you look for another hospital, I suggest you look for a research hospital which has plenty of patients on trials.

Something else you might do is ask your onco and GP if they would object to you taking metformin, and if not, ask for a private prescription. I think it's much cheaper than even the prescription charge in England. However, I would strongly suggest you start monitoring your blood glucose levels as I suggested earlier if you are going off-piste, and that you are keeping records might help convince them you know what you're doing.

Posted 30 Dec 2019 at 11:32

Thanks again Andy - I have established that I am not eligible to join the Stampede Trial because I do not meet the eligibility criteria, and in any event, not all participants in the trial receive the treatment so that is no good.  I want to start monitoring my blood glucose as suggested and so wonder what sort of monitoring system is best and least invasive.  I have seen that there appear to be some completely non-invasive systems available but wonder if you have any suggestions about these?

Posted 30 Dec 2019 at 12:18

Thanks Lyn - I have asked two oncologists and both say I am definitely not eligible and have proved this with the eligibility criteria.  The oncologists are unwilling to prescribe because it does not meet NICE guidelines for PCa and they could be struck off if something went wrong (ie hypoglycaemia).  And as I am not currently diabetic (my blood glucose level appears constant at 41 just below the lower pre-diabetes level (42).  Maybe that will change with the hormone therapy as Andy says, I dont know.  But a private prescription is what I have been asking for - and they are all scared of providing it in my case.  I have asked a urologist who says that he is going to try to justify this with regard to the Richards study data for me but I am not holding my breath.

Posted 30 Dec 2019 at 12:29

I would guess non-invasive systems would be stupidly expensive when you only want about one sample/month, but I never actually looked at them (they probably weren't around at the time). A finger prick once a month really isn't an issue, and it's not painful.

I use an Accu-Chek Aviva Nano which is long obsolete, but test strips are still easy to buy (it might be they're still used in current models). If you buy a meter, make sure it reports in the right units, mmol/L for the UK. US meters and some other countries use different units, and people sometimes buy these by mistake online. If you buy one in a pharmacy like Boots, it will be a UK one. It will probably come with some test strips, but the test strips have a limited shelf life. If you're only testing once/month, buy 10-packs and check the expiry date is far enough out that you will be able to use them all. You will also need replacement lances for the finger pricker.

I do monthly fasting tests - in the morning having not eaten for 12 hours. The occasional non-fasting test is good to check too (2 hours after a meal), but I don't think you can sensibly graph those as meals are not going to be sufficiently consistent.

Posted 30 Dec 2019 at 12:44

Oh - I have been lead to believe that you have to do tests every day several times a day when on Metformin in case the blood sugar drops to a very low level at different times of the day/night but what you say suggests otherwise.  Perhaps initially when going on the drug you have to monitor more closely?

Posted 30 Dec 2019 at 13:55

What you say may be true for some anti-diabetic drugs, but my GP said metformin can't give you a hypo, which was one reason he was happy to give it to me. (I've since seen this mentioned in articles about metformin, which say metformin alone has a negligible chance of generating a hypo.)

My glucose level was near the bottom of the normal range before I started taking Zoladex, but Zoladex pushed it near the top of the normal range, and that level probably gives me additional protection against a hypo. I'm currently taking a dose which has pulled it down to just above the centre of the normal range. My GP knows I'm monitoring it, and that might also have factored into his willingness to let me have it, and let me choose my dose (currently half the limit he's set). He might have been less willing for a patient who was not monitoring his glucose level, and couldn't show a historic graph of it rising as soon as I started on Zoladex.

Collecting data is good. It gives you insights into things you otherwise wouldn't have seen. (This was my approach in my job of looking after loads of computer systems - I simply turned this approach on myself instead.)

I also spotted Zoladex was increasing my blood pressure in the same way, flagged this up to my GP, and my blood pressure meds have been adjusted appropriately. These are both known side effects of many HT drugs. I carefully monitor my weight and body composition, exercise, breast growth, and other things like sexual function which the various treatments can affect. A couple of urologists have looked through the data and said they just never see that level of information from patients, and it's really useful to know this for setting expectations of future patients. It's also useful for me when counseling patients, although somewhat limited because my sample size is just one (me), and HT symptoms vary considerably between people.

Posted 30 Dec 2019 at 15:17
Which criterion do you not meet?
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard

Posted 30 Dec 2019 at 15:41

Well - I have shown the criteria below

I am not newly diagnosed so 1 does not apply and anyway I have Gleason 3+4 with a pre-prostatectomy PSA of 7.4.

I am not diagnosed currently as node positive or metastatic.  I have microscopic disease.

I recently had salvage RT following a relapse to 0.13.  I had a pre-prostatectomy PSA of 7.4 but dont know the doubling time because it was my first PSA or even whether these PSA's relate to pre-surgery, pre-Radiotherapy.  I must say that this part confuses me a bit so worth asking the oncologist about again I think.


They criteria are:

1. High Risk Newly Diagnosed non-Metastatic Node Negative Disease


At least 2 of:    T category T3/4, PSA>=40ng/ml or Gleason 8-10

Intention to treat with radical RT (unless a contra indication)


2. Newly Diagnosed Metastatic or Node Positive Disease


Previously Radically Treated now relapsing (Prior Radical Surgery and/or Radiotherapy)

At least one of:

PSA >=4 and rising with doubling time <6 months

PSA >= 20



Posted 30 Dec 2019 at 16:09

I would have fitted Criteria 1 at the time I started.

T3a, PSA 57 [Gleason 7]
Intention to treat with radical RT (which has since happened).

Criteria 1 is almost the definition of a High Risk patient, except that for N0M0, it requires 2 of the high risk categories instead of just any 1, but I do have 2 of the high risk categories.

I didn't check the criteria at the time, but my onco said I might be able to do the STAMPEDE trial if I wanted, although I would have been randomised with a 1/3rd chance of getting a placebo. It might be that given your pre-salvage diagnosis doesn't qualify, your prognosis post salvage RT is now so good the metformin is unlikely to help.

Posted 30 Dec 2019 at 16:14

Well there is no point in joining a trial where you've got a 1/3rd chance of receiving a placebo unless you are out of options.  That random trial system is really cruel!

Posted 30 Dec 2019 at 16:21

My point is that the research data appears to indicate that Metformin is safe, and has a beneficial effect in conjunction with ADT when used in the long term, to prevent metatstatic disease and increase survival, hence my reason for wanting to take it now rather than waiting.  But the oncologists don't see it my way.

Posted 30 Dec 2019 at 16:23
Ah, my mistake; I thought you were node positive. I can’t see the point of you chasing metformin when you are only going to be on HT for a short time.
"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard

Posted 30 Dec 2019 at 16:25

Originally Posted by: Online Community Member

Well there is no point in joining a trial where you've got a 1/3rd chance of receiving a placebo unless you are out of options.  That random trial system is really cruel!


Some men on here take the opposing view; that the benefit of closer monitoring is worth it even if you end up with the placebo, plus it hopefully contributes to improved care for men in the future. 

"Life can only be understood backwards; but it must be lived forwards." Soren Kierkegaard

Posted 30 Dec 2019 at 16:25

No - Ill be on ADT for 2 years (now 1 year 8 months left) so I dont agree.  If it were only 6 months I would agree with you.

Posted 30 Dec 2019 at 16:29

Sorry I am not equipped to argue against randomised trials and would not criticise anyone for taking part from an altruistic perspective - I am talking from a purely selfish perspective of course.

Posted 30 Dec 2019 at 20:18
I have PM'd you.

Gleason 6 = 3+3 PSA 8.8 P. volume 48 cc Left Cores 3/3, Volume = 20% PSA 10.8 Feb '19 PSA 1.2

Jan '20 PSA 0.3 July '20 0.1 Jan. 21 < 0.1

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