Metformin’s herbal history


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Today we feature a blog from one of the teams here at Diabetes UK – The Library and Information Team. Here they tell us about the history of Metformin…

Diabetes UK is occasionally asked about the evidence for and effectiveness of a variety of alternative treatments such as herbal remedies or vitamin supplements. Although most of these are a waste of money (never believe anything that says you can ‘reverse diabetes’ – see the example in this spoof version of a ‘miracle cure’ website), plants genuinely do contain a variety of interesting chemical compounds and many are used in medicine.

Traditionally-used medicinal plants can contain many different active ingredients in varying concentrations. Some are harmful at low doses and some at higher doses. These chemical constituents can interact with prescribed medications and cause problems and these are some of the reasons that Diabetes UK does not recommend the use of a herbal remedy for the treatment of diabetes without consulting a doctor.

The Library and Information team at Diabetes UK receives a number of medical and scientific journals. We sift through the articles and provide a current awareness service for our colleagues. Recently we received a copy of the journal Diabetologia which had a lovely photograph on its cover of a plant called Galega officinalis (also known as French lilac or goat’s rue). Having recently had our 75th anniversary (Diabetes UK was founded in 1934) and being aware that it was really just one lifetime ago that insulin was discovered (1922) it was a nice reminder that many of our modern drugs have come from herbal traditions.

Galega officinalis is the ‘root’ of metformin, one of the most commonly used medicines for Type 2 diabetes. Although the plant itself was in use for hundreds of years, for a variety of medicinal and agricultural purposes (eg used to increase the milk yield in cattle) Galega officinalis is considered to be rather toxic and in several US states is defined as a ‘noxious weed’ that is harmful to grazing cattle. It was well known in mediaeval times as a treatment for symptoms for what we’d now call diabetes, including excessive urination. From the late 1800s the plant began to be investigated as the source of a treatment for diabetes.

The plant contains a variety of chemically similar components which vary in their levels of toxicity and ability to lower glucose levels. Guanidine compounds are more toxic and can cause plummeting glucose levels but the guanidine-like compound galegine lowers glucose levels less dramatically with slightly less toxicity. However, these native plant compounds are still not safe enough for use as a treatment.

In the early part of the 20th century chemists investigated derivates of these guanidine-like compounds, developing a range of ‘biguanide’ drugs, although advances in insulin therapy put these drugs on the back burner for a while. In the 1950s these biguanide drugs came on the UK market for Type 2 diabetes, but the one that stood the test of time is metformin (sold as Glucophage which means “glucose eater”) – it has been in use in the UK since 1958, though it was only licensed in the US in 1995.

Further reading
Witters, L (2001) The blooming of the French lilac Journal of Clinical Investigation
108 (8): 1105-1107.

HCS Howlett and CJ Bailey (2007) Galegine and antidiabetic plants in Metformin: the Gold Standard. A Scientific handbook; Chichester: Wiley.

Bailey CJ and Day C (2004) Metformin: its botanical background Practical Diabetes International 21 (3): 115-117.

Hadden DR (2005) Goat’s rue – French lilac – Italian fitch – Spanish sainfoin: Galega officinalis and metformin: The Edinburgh connection Journal of the Royal College of Physicians of Edinburgh 35 (3): 258-260.

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It is interesting reading about other diabetics’ medications. I was diagnosed type 2 at the beginning of 2008. To update my knowledge about diabetes (which I last studied in the 1980s) I studied two short courses with the Open University: Diabetes Care SK120 and Understanding Cardiovascular Disease SK121. I would recommend these to any diabetic who wants to learn more about their condition. That said, studying is one thing but actually having the condition brings greater understanding. One very important thing I have learned is that we diabetics need to think about our condition more holistically. Medication is something we need to have and get the best control of, but it is only one action among many we need to think about taking, and they all seem to be interconnected.

Exercise is very important. I was able to cut my metformin dose from 4x500mg to 3 x 500mg when I went on a condition management course (free gym classes). The proof: my HbA1C improved.

The right amount of regular sleep and managing stress seems equally important. When I get these wrong my blood glucose goes more out of control, and that happens quickly.

Also whenever I am ill my blood glucose goes badly out of control and I wake up hyperglycaemic; sometimes I get neuropathy in my feet from this. I am now more aware of the need to avoid flu and avoid cuts and grazes. I passed my Open University courses SK120 and SK121, but ironically did not take some of what I had learned anywhere seriously enough. As a consequence in 2009 I spent a week in hospital getting IV antibiotic treatment for septicaemia. It also took several months to get over that, and among other things brought back my gout condition because I had lost a lot of fluid through swetting with the high temperature. Although I previously managed my uric acid with diet I now take Allopurinol for that – I don’t want to have gout and hyperglycaemia at the same time again if I can help it.

Diet is clearly important. In 2010 I had raised tryclicerides: more than 7.0 mmol/L, also following a bout of illness. I know that is very high and have made an effort to reduce it using diet, which is working, i.e. two further blood tests showed a drop to less than 6.0 mmol/L. I am hopefully heading to a normal reading of less than 2.0 mmol/L. The problem is the time I have to wait between tests which means I can’t be sure what I have achieved from my efforts at improving my diet.

I believe more regular testing is important to improve control – a lot of damage can occur in a few months. I want to avoid more serious consequences of my condition as long as possible. I only use my blood glucose meter when necessary, and I think I am a good judge of that now. I attended the International healthcare trade show in Dusseldorf in November 2010 (Medica) and found many companies are now manaufacturing testing meters that do testing for blood sugar, cholesterol, and uric acid using the same meter. I would like free test strips from the NHS for cholesterol measurement as high cholesterol can affect the glucose reading (according to manufacturers’ literature). That makes sense to me. I think it should make even more sense for the NHS to prescribe these to diabetics if they have very high cholesterol. I would gladly cut my consumtion of blood glucose strips if I could have the cholesterol testing strips which are approximately the same price each. I guess there is a long way to go before the NHS really listens to patients. In 2010 when I worked for the NHS at PCT level in West London I could see that beginning to happen, but I suspect things may be going backwards since the announcement of the dismantling of PCTs. I contacted the PALS unit of my local PCT several months ago asking about testing strips and still have not been sent an acknowledgement that my email is being looked at.

Boy, I thought it was just me! I was taking 2000g a day and after a while felt the effects. I forgot to take my pills one day and only had 1000g – no tummy trouble. So I tried 1000g for a few days but the skin between my fingers started to dry out – a sure sign for me that blood sugars were on the up. So to counter this I popped an extra 500g and everything seems to be at a nice stable level. Exercise helps to regulate things too. In fact I haven’t been to the gym for over a week and have noticed levels rising! I wasn’t going to blog about this as I didn’t realise how common it is, but now I will. Terry, you aren’t alone my friend.

Hello Terry

Thank you for the comment. I’m not medically trained so please take the following text ‘for information purposes only’ and speak to your doctor if you want to investigate any of the suggestions further. I would also echo my colleague’s suggestion to give our Careline a call, or you can email them on careline@diabetes.org.uk

A range of possible gastrointestinal effects with metformin are unfortunately quite common as Lee mentions, however rarely as severe or for as long (they usually resolve in most cases). Gastrointestinal disturbances can *also* be a consequence of diabetes itself, as well though. The movement of food through the gastrointestinal system is under the control of a variety of muscles – these in turn are also controlled by nerves and if there is nerve damage then this *can* be one of the areas affected.

I don’t think a rectal exam would necessarily indicate if this was the explanation, I believe endoscopes and possibly barium
meals can be involved to find out how quickly, or slowly, food passes through the body. We have some information on our website about ‘autonomic neuropathy’. See also this page from CORE (the charity for digestive disorders) on ‘diabetic gastroenteropathy’.

There are several types of metformin available – I’m not sure by how much the various formulations vary but this may be worth discussing with your doctor as well, for example there is also a ‘slow release’ form of the tablets. One manufacturer of standard metformin recommends that it should be taken ‘in 2 or 3 daily doses during or after meals. A slow increase of the dose may also improve gastrointestinal tolerability’. If you’ve been taking it for a while though, perhaps this isn’t working for you. In addition to metformin by itself, there are separate formulations which pair metformin with another drug such as:- metformin + pioglitazone (available as Competact) metformin + vildagliptin (available as
Eucreas) metformin + sitagliptin (available as Janumet).

I don’t think we have any information that specifically compares metformin with insulin but we do have information about the two treatments (and other diabetes medications as well). Please see the Treatments section of our website – note the pink menu bar on the left hand side where you can look at different treatment types. For more detailed information we do have booklets – one is available as a free download, “Type 2 diabetes medications” and one costs £2 (plus p+p) – “Treating your diabetes with insulin”.

Ironically gastric disturbances can both be caused by and contribute to worsening glucose control yet can make it extremely difficult to get glucose levels under better control. However, there are many opportunities to improve things with appropriate medical help.

Kind regards,

Jo

Jo Brodie
Science Information Officer
Library and Information Team
Diabetes UK

i have been on metformin of varying doses since shortly
after being diagnosed in 2002. i now take 2x500mg in the morning
along with gliclazide and injecting Byetta. I then take 1x500mg in
the evening along with Byetta again. The metformin is the slow
release version now. I had digestive issues with metformin but
persevered and found that a daily ACTIMEL helped greatly!!!! the
fear of embarrassment is great but i found that avoiding large
amounts of nuts or coffee helped also.

I’ve been taking metformin for about five years. I haven’t had any side effects from it, but I found it stopped being effective on its own after a year and now have to take gliclazide as well.

I’m Type 2 also and was on 2000mg/day also and with weight
loss, exercise and a change of diet/lifestyle, this was reduced to
1000mg/day and now none at all – which is great. However, I never
experienced Terry’s difficulties – if anything, I went the other
way and have, in the past week, been on medication from my GP for
constipation which has become progressively worse over the past 6-8
months. Initially, when discussing these problems with my
GP/Diabetes nurse(s) it was considered that Metformin could be the
cause. So I suppose it’s individual specific.

i take 4 meformin once a day at night after eve meal
normally and have inserlin in the mornings i have no problems at
the moment feel sorry for terry

Hello, I do sympathize with poor Terry’s problem. I too
suffer same said symptoms but thankfully (more often than not)
there is a toilet not too far away. I also did not “read the label”
with regards to the side effect of metphormin but in many respects
I always read the leaflet/s or paperwork with anything and
everything now. (Just to be on the safe side..LOL) I could go on
insulin but the only career I know is as a HGV/LGV Driver and this
would mean me having to relinquish my licence for said job. I would
obviously keep my car licence but still have to have more frequent
medicals. The upshot to all this..?? Well, I’ll keep my HGV/LGV
Licence and always know that there is a toilet near me and suffer
in silence and carry plenty of air freshener.. Merry Christmas
everybody and to you guys at D.U.K..

Interesting article. I have been type2 diagnosed for about two years now. I am on 1000mg a day of Metformin.

Unfortunately for Terry his body doesn’t seem to cope well with it. While mine does cause stomach upset, what most people would call the runs, there is in the main no “urgency” about it. That can’t be said about some of the blood pressure meds I have tried.

Metformin has kept my blood sugar at almost text book levels since I started on it, I can’t realistically ask for much mote than that.

The leaflet and advice with Metformin does state stomach upset as a likely effect, people weigh up the pros and cons, most feeling it’s a better option than insulin and a minor inconvienience to slow the onset of organ damage and the rest.

Poor Terry paints a glum picture about Metformin but I would guess his severe reaction is only experienced by 1:10 maybe 1:100 or more.

Hi Terry,

Thanks for the comment – might be a good idea to call our Careline on 0845 120 2960 and ask them about this too. They’ll have given advice to many on this subject so should be able to talk you through Metformin vs insulin and give you the info you need.

Hope you have a good Christmas,

Diabetes UK

I take Metformin and it has ruined my social life. I am type 2 and take 1000mg twice a day. The Metformin has upset my bowels so much that I rarely leave the house after I had a very embarrassing situation in the middle of my local High Street. I lost control of my bowels completely and the obvious happened. I then had to get back to my car and home for a wash and shower, I have never felt more humiliated. I had just started Gliclazide as well and stopped them immediately after that episode as I thought it was them that had caused the problem. Unfortunately I still have the problem and when I’ve got to go, I have to go, so a toilet has to be near. I relayed all this to my GP and he did give a rectal examination and all was fine. He said he may have to consider Insulin as the Metformin is causing me problems so after Christmas I will go to the Hospital Diabetic dept and try and get on Insulin. I don’t know much about it but if it stops by bowels from being out of my control it will be worth it.
I am 65 and a male and have been a diabetic on Metformin for about 5 years and it has been the worse 5 years of my life! I would like to know if there is a booklet or some written advice on Metformin verses Insulin. I don’t care about injections; I just want to get my life a little back to normal.