Metformin and B12

Back in December 2006, Amy Campbell wrote in her blog about the possibility of the popular diabetes drug metformin causing vitamin B12 deficiency. In a follow-up comment, she mentioned that taking calcium supplements might help to remedy this deficiency. The information spurred an outpouring of comments and questions from concerned readers, so those of us on the magazine staff decided to investigate the matter further.


Our Q&A editor, Alwa Cooper, contacted Mariejane Braza, MD, and James F. Hanley, MD, of the UTHSCSA-Regional Academic Health Center in Harlingen, Texas, who had recently conducted some research on the topic of metformin and vitamin B12 deficiency. As published in the November/December 2009 issue of Diabetes Self-Management, here is their answer:

“Metformin is an important and effective medicine for the treatment of Type 2 diabetes; however, with prolonged use, as many as 30% of the people taking it develop a B12 deficiency. It has been our experience that not all physicians are aware of this association.

Detecting B12 deficiency can be difficult, because the early symptoms, such as fatigue or loss of appetite, may be subtle. Other symptoms, such as numbness or tingling in the hands and feet, may be assumed to be complications of diabetes. In a study that we conducted, peripheral neuropathy (nerve damage in the hands, feet, and legs) was more common in subjects with both Type 2 diabetes and B12 deficiency than in those with Type 2 diabetes alone. Prior to our study, it was presumed that these participants’ neuropathy was a complication of their diabetes. We felt, however, that it was not clear whether this was the case or whether B12 deficiency had played a role in or caused the development of the neuropathy.

Testing for B12 deficiency may not always be straightforward. People with a severe B12 deficiency usually have a type of anemia characterized by enlarged red blood cells, a low platelet count, and even a low white blood cell count. However, this type of anemia may not be present in people with a moderate or minimal B12 deficiency. For this reason, direct measurement of B12 levels in the blood (serum B12) is considered the gold standard for diagnosis. However, even this test result may require some expert interpretation, because the level of serum B12 does not always reflect the amount of B12 available to the body’s cells. When the serum B12 level is low, it is overwhelmingly likely that there is a deficiency; however, a low-normal value may also represent a deficiency. In that situation, some experts recommend testing levels of methylmalonic acid and homocysteine; when there is a B12 deficiency, both of these are usually elevated.

Classically, the treatment for B12 deficiency has been intramuscular injection of a common form of B12 called cyanocobalamin, beginning with priming doses (at first daily, then weekly) then monthly doses for life. Another option is oral cyanocobalamin in relatively large doses; in several studies, this approach has been effective in treating the deficiency, no matter what the cause. Oral cyanocobalamin is also inexpensive and rarely causes side effects.

The possible effectiveness of using calcium to reverse or reduce the effects of metformin on B12 deficiency is based on the finding of a 2000 study that demonstrated that people taking metformin had reduced absorption of vitamin B12 that could be reversed with the use of calcium in the form of the over-the-counter antacid Tums. The research suggested that metformin interfered with absorption of vitamin B12 in the small intestine, a process dependent on calcium—thus requiring supplemental calcium to regulate it. But in clinical practice, it is not as clear whether taking extra calcium is enough to avoid a deficiency.

Since our study was done, some of the health-care providers at our center have decided to prescribe oral cyanocobalamin to all of their patients on metformin, making it unnecessary to monitor them for B12 deficiency.”

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  • Steven Leitner

    Why do your articles always eliminate the essential information that could help a reader: What potency oral cyanocobalamin would be adequate to build blood values? (If you’re going to give info why not give info that is useable?)

  • Tony

    Years ago I heard & read that the preferred form of B12 for Peripheral Neuropathy & Type 2 Diabetes is Methylcobalamin NOT Cyanocobalamin! The blend of B6(Pyridoxine HCL), B12(Methylcobalamin) & Folic Acid works for me. I’ve found the cheap B12’s on the market (Wal*Mart,Safeway etc..) that contain Cyanocobalamin don’t do a thing in relieving my Idiopathic Neuropathy zaps,twitches & tingles. Wife has Type2 & uses metformin.
    I first learned about Methylcobalamin from an article about FELINE DIABETIC NEUROPATHY & it referred to
    The article stated that unlike regular B12 (Cyanocobalamin), METHYLCOBALAMIN is active in spinal fluid. Because of this, it’s able to help heal the damaged nerve cells and restore the signal to your (CATS) weakened muscles.

  • allan

    I can’t take calcium supplements.
    I however can take Strontium, and do.
    By the way calcium supplements never worked on me when I did take them.

    Since started with Strontium supplements, my bones are stronger, my joints don’t hurt anymore, and I can exercise without pain.

    I also have an aura of well being. A more positive outlook on life at 73.

    good luck to all.

    los angeles

  • Robert Labron

    I am more confuse after you article, I just got put on Metformin because my homone shot for my prostate Cancer elevated my blood sugar level above 200. So the Metformin 500mg,half tablet in am and half in pm.Now in my case,what should I take to keep from having a B12 Cyanocobalamin problem.,

  • Anne

    Dr Whitaker in his booklet ” The Truth About Diabetes and How to Reverse It Now” recommends 150mcg of B12. I am taking 100 mcgs of regular B12 and get 25 mcg in my multivitamin. I have been following “Prevention’s Diabetes Diet Cookbook” for over a year and had not lost weight. Since I started taking B12 3 weeks ago, I have started to lose weight. Best of all my belly is sliming down. My alterationist is making a lot of money on me.
    I also take Calcium tablets.

  • FreeloaderFred

    Interesting start.
    I hope the center’s health-care providers got some results.
    Anything useful? Any how-to’s? Any gotchas?
    When tomorrow comes, it would be nice to know what tomorrow brought. Please?

  • Marcie

    Tony —

    > The blend of B6(Pyridoxine HCL), B12 (Methylcobalamin) & Folic Acid works for me.

    Amounts/mg of each?

  • emma1267

    Good evening

    I was on Metaformin a few years ago and my body never adjusted to it. So they put me on Glumetza which is a form of Metaformin and doesn’t cause the side affects that Metaformin did. I am wondering if I should be concerned with my B12 count. I am always very tired among other things.

  • Barb

    my husband has Type 2 diabetes and has been on Metformin for several years. He began having short term memory loss, lack of concentration, tiredness, etc. He was first thought to have the beginnings of Alzheimer’s, but MRI proved negative. Then, depression was investigated and medication tried, but to no avail. Finally, his doctor decided to try Bl2 shots, and all symptons have nearly disappeared. Would have been nice to have this taken care of when it first became a problem!

  • Ingrid Strauch


    We would suggest that you speak to the doctor who prescribed metformin for you about whether you should take vitamin B12 supplements. Your doctor is the best person to evaluate your personal medical needs.


    Glumetza is simply an extended-release formulation of metformin, and it, too, can affect your body’s absorption of vitamin B12.

  • Dick

    When I was a teenager I had to take B12 injections from my doctor. At age over 60 I’m type 2 diabetic and take Metformin. Should I be concerned about the B12 now?

  • Craig

    Anybody want to answer Steven Leitner | Jan 27, 2010 at 3:43 pm? His question was about dosing.

  • Ingrid Strauch

    Hi Craig (and Steven),

    We have forwarded Steven’s question about dosing to the researchers mentioned above, and when we get an answer, we’ll post it here.

  • Donna

    My husband and I are both taking metaforim… I take 2 in the a.m. and 2 at nite… along with glimpride… 2 and 3 a.m. and p.m. I have been taking it for several years, and the dosage has just been increased this past year. I do have tingly feet, and itch all over from dry skin I thought, which is a diabetic happening I have been told. Now I wonder if I should get on the B-12 and if so what dosage… I do not take any vitamins, but do take a once a week calcium pill that was prescribed by my Dr.

    My husband is on just 1/2 metaforim twice a day and glimepride, but does take lots of other meds, and vitamins. I have a hard time swallowing, where he can take all his in one gulp. Size of pills is definitely a problem for me.
    We are in our 80’s, but very active and we feel pretty healthy… somewhat over wt in parts…tummy especially.

  • Robert

    I’ve been taing Metformin for about 10 years.
    I’ve recently heard that someone on this drug
    usually has to switch to insulin shots after the
    10 year mark. Anyone heard anything like this from the medical profession?

  • Toni

    I have been taking Metformin for 15 yrs. ai addition to Glipizide and now I am on insulin. I take 1000 mg. in morning and one at night and I am so confused that I am about to just quit taking them and take my chances. My Mom and Dad 2 sisters and a brother has had type 2 diabetes and it seems that when they started insulin they went downhill real fast, They have all passed away except myself and my brother who is getting real bad so I am so confused that I don’t know what to do. I hope someone can help me. Thank you.

  • Dino

    I took 500 mg Metformin and Gliburide 2.5 mg once a day for about ten years. My hair started to fall and my fingernails are all gone. I informed my doctor and he ignored my complain. As well, sometimes I go three days without sleep, have gained weight and feel a bit depressed.

    Last January the pulmonary Dr. prescribed Prednisone for a respiratory problem and my sugar count went over 300. My family doctor uped the Metformin to 1000 mg twice a day. I started itching all over really bad; I had to stop the Metformin. Doctor prescirbed one a day Actos, & he increased the Glyburide to 10 mg. My sugar is still around 200, and am still itching,although not as bad.

  • neil

    American Docs make much more money than in other countries. Much much more. Especially specialists. I had mouth cancer and had seen 3 docs about it and they all said not to worry about it and it will go away. A few weeks later on a vacation to the EU I thought I’d get another opinion and sure enough it was Cancer.

  • neil

    Thanks to comment boards like this where we can stumble across important info to help us steer our course lest we become part of that 200 thousand statistic. Doctors in the EU educate their patients rather than slowly kill them with incompetence. We used to be a great country or so the anthems of our childhood conditioning used to hammer in.

  • Mary

    I have been on Metformin for a couple of years. Read where it could cause a drop in B12 levels. Requested my doctor order lab for it and sure enough I was low and continue to work to get it within normal range. If you take metformin ask your doctor to investigate.

  • Edwin Casimero

    My wife has been ill for 2 weeks now. Doc says it is B12 deficiency. Thank you for posting this. This will encourage her.

  • AL

    I wouldn’t waste my time with the cyanoB12 ever again. After diagnosis with B12 deficiency, I suffered unnecessarily for over 4 years with continued pain and worsening symptoms even though cyanoB12 injections jacked up my serum B12 levels considerably. Turns out even if there is a lot of serum cyanoB12 that doesn’t mean your body is converting enough of it to the active methyl form for actual use. It wasn’t until I used methylB12 instead that I saw any real improvement, and by then the B12 deficiency had cascaded into several other problems! Don’t settle for cyano; demand methyl! Why take the chance your bloodwork will mislead your doc and your body won’t get any better, when for just a few dollars more you can be certain you are injecting something your body will actually use? And there is the option of sublingual methylB12, though it isn’t as well absorbed as injections. And finally, once you get your B12 levels up, methylB12 injections into fat give a nice time release dose for maintenance, as opposed to muscular shots. Since I am on my soapbox, here is a plug for the other most important thing in my opinion–vitamin D, check it and supplement to get your levels up! I wish you well.

    • MarLookinTillSheSeesThoseEyes

      AL, while I feel your suffering, some other people may not have the difficulty absorbing the B12 in their serum or that they supplement with oral B12 that you most certainly do. For that absorption issue, mythl IS a way better choice like you stated but for others, oral supplementation without needles is a better choice. Some people refuse anything delivered via needles, others again, whose small intestines are able to absorb the oral supplementation simply aren’t going to elect getting shots when they aren’t required to deliver their cells the B12.

  • vicky

    Yes! Metformin is an important and effective medicine for the treatment of Type 2 diabetes.

  • henry grubel

    any physician wh writes an rx for metformin shuld also provide patient with IM B12 shots.

  • Christine Kaye

    Very interesting. Just yesterday I talked to my doctor about my lack of appetite and nothing was said about B12. I have been on Metformin for two years and eating has become increasingly difficult. Due to side effects, I had to cut back my meds, which resulted in a slight increase in my blood sugar. I became determined to get off Metformin, and all diabetes medication. After a week and a half on a reverse diabetes program, my daily readings are 88-92 and have cut my meds in half with hopes of curtailing them soon. I definately will look into B12 to see if it can help me regain a healthy appetite!

  • Tina

    Those of you who are diabetic and are on oral medications like metformin, glyburide, etc. please read or get information about Dr. Julian Whitaker’s book, “Reversing Diabetes”. My husband has been type 2 diabetic for over 14 years. His blood sugar is out of control even though he’s been on medication all this time. The doctor has been talking about putting him on insulin. My husband’s mother was put on insulin and within 2 years she died. I don’t want this for my husband. Dr. Whitaker’s book is very informative about not only the negative effects of insulin and oral drugs but the vitamins and other natural supplements and dietary changes and exercise you can make to perhaps reduce or eliminate the need for oral medications.
    I urge you to arm your self with knowledge and make informed decisions with your doctor for your sake or the sake of your loved one.

    I have become convinced that if I don’t help my husband make the natural changes recommended in the book my husband will be put on insulin and his quality of life will suffer tremendously.

    To your good heath without drugs!

  • Rose Young

    I was put on metformin now my hair and skin is so dry what can I do help me.


  • Jack

    When I became diabetic, started taking 1000 mg of Metformin HCL, twice a day with Glyburide once a day. Then they changed from Glyburide to Glipizide. Now I’m still taking Metformin HCL 1000 mg twice a day, Glargine Insulin 36 units, and Aspart Insulin 36 units total (12 units 3 times a day). After the first year of having diabeties, I got neuropathy in both feet (started with the toes). I see a Primary Care Physician, a Diabetic Specialist, and several other doctors. It was my Podiatrist who did the research and told (and show the documentation) me about Metformin causing a deficiency of B12, which could result in getting neuropathy. I’ve read statements saying the damage of neuropathy is irreversible. I’m beginning to believe this to be true. Since he told me this, I have been taking over 300 mcg of B12 daily, and getting an injection once a month. This has not helped. In fact, the neuropathy has gotten worse. It has taken over most of both feet, and my left arm, from the elbow to the finger tips. This has happened over 5 years. I’ve done what all my doctors have told me to do. I’ve lost over 60 lbs, cut out all the bad foods, kept my glucose levels down, and take all the medications required. And yet, still going downhill with all the side effects. I had told my Diabetic Specialist about what my Podiatrist had found, but even after reading the documentation, she still didn’t think that the Metformin was the cause of the problem. So, I quit taking the Metformin for one week, and my feet actually felt a little better. But the good doctors still say I need the Metformin. The good things it does out weighs the side effects. It’s not their feet. I am presently taking a total of 12 vitamins and prescription medicines in the morning, and 10 in the evening, along with the insulins. Two thirds of the medicines are for medical ailments. The other third are to counter the side effects caused by the first two thirds. Modern medicine. Amazing.