Metformin and B12 Deficiency

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Metformin and B12 Deficiency

Metformin (brand names Glucophage, Glucophage XR, Fortamet, Riomet, Glumetza, and others) is a popular and highly effective oral diabetes drug used to help manage type 2 diabetes. For most people who have type 2 diabetes, metformin is the first drug that is prescribed to help manage blood sugar. It’s also used to treat prediabetes, gestational diabetes, and PCOS (polycystic ovary syndrome).

How metformin works

Metformin works by lowering the amount of glucose made by the liver, by reducing the absorption of glucose in the intestines, and by making the body’s cells more sensitive to insulin (meaning, the body responds better to insulin). Unlike insulin or sulfonylureas (a class of diabetes pill), metformin does not cause hypoglycemia (low blood glucose).


Other benefits of metformin

In addition to helping manage diabetes, metformin also has some other beneficial effects in that it may help lower blood fats and promote a small amount of weight loss. Metformin’s potential benefits don’t stop there — researchers think that metformin might protect against kidney disease and dementia.

Who can take metformin

Metformin can be used with most other diabetes pills, with insulin, and with noninsulin injectables, such as GLP-1 inhibitors. Side effects of taking metformin are relatively rare, the most common being bloating, nausea, and diarrhea, all of which are temporary for most people. Some people shouldn’t take metformin, including people with stage 4 or 5 kidney disease, liver disease, and people with type 1 diabetes.

Vitamin B12

A potential downside of taking metformin is the link between long-term metformin use and vitamin B12 deficiency. Vitamin B12 plays many important roles in the body, such as keeping your blood cells and nervous system functioning properly. This vitamin also prevents megaloblastic anemia, a type of blood condition that causes fatigue and weakness. Researchers are studying the effect of vitamin B12 in possibly preventing dementia and reduced cognitive function.

Foods that naturally contain vitamin B12 include meat, poultry, fish, eggs, milk, and beef liver. Some foods, such as certain breakfast cereals and nutritional yeast, may be fortified with vitamin B12.

Who is at risk of B12 deficiency?

People who may not get enough vitamin B12 or who have trouble absorbing it include:

  • Many older adults
  • People who don’t make enough hydrochloric acid and intrinsic factor in their stomachs
  • People with pernicious anemia
  • People who have had some types of stomach or intestinal surgery
  • People with digestive disorders, such as celiac disease or Crohn’s disease
  • People who follow a vegetarian or vegan eating plan

Signs of B12 deficiency

Weakness, fatigue, heart palpitations, appetite loss, weight loss, and numbness or tingling in the hands or feet (signs of nerve problems), depression, confusion, dementia, and soreness of the tongue or mouth are signs of a possible vitamin B12 deficiency.

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How metformin and vitamin B12 deficiency are linked

Research shows that people who have been taking metformin long-term are at risk for vitamin B12 deficiency. A study published in the April 2016 Journal of Clinical Endocrinology and Metabolism looked at more than 1,000 subjects who had been taking metformin for about 12 years; of those, 13% had an increased risk of vitamin B12 deficiency. Another study showed that people with type 2 diabetes who took more than 1,000 milligrams (mg) of metformin for four or more years were especially at risk for a vitamin B12 deficiency. It appears that the longer someone takes metformin and the higher the daily dose of this medication, the greater the risk of developing a B12 deficiency.

Why does vitamin B12 deficiency occur with long-term metformin use?

It’s thought that metformin possibly interferes with absorption of the vitamin in the digestive tract. Of note, the body stores between 1,000 and 2,000 times as much vitamin B12 as one would typically eat in a day; for this reason, symptoms of vitamin B12 deficiency can take several years to appear.

The American Diabetes Association recommends that people taking metformin periodically have their B12 status assessed, as a deficiency may contribute to anemia or peripheral neuropathy. Vitamin B12 status is assessed by a blood test.

Treating a vitamin B12 deficiency

A vitamin B12 deficiency can be treated in a number of ways. A more serious deficiency is generally treated by vitamin B12 shots, initially every other day and then once per month, or high-dose B12 pills. Milder deficiencies may be treated with a standard multivitamin, an oral supplement, or with a nasal spray.

One study found that people taking metformin who took a daily multivitamin supplement had a 50% higher serum B12 level compared with those not taking a supplement. (A standard multivitamin contains between 5 to 25 micrograms of B12). However, another study found that most multivitamin supplements don’t have enough vitamin B12 for those who take metformin. The authors concluded that long-term use of an oral B12 supplement might be needed to maintain an adequate B12 status. Also, people who take certain medications that affect gastric acidity, and elderly people with diabetes, may need a B12 supplement in a higher dose. (Vitamin B12 supplements typically contain 500 to 1,000 micrograms). For more information about vitamin B12, including daily requirements, visit the National Institutes of Health website.

What you can do

  • If you have been taking metformin for several years, ask your health care provider to have your vitamin B12 level measured, and ask what your level should be.
  • If you have symptoms of a vitamin B12 deficiency, including neuropathy, let your provider know and ask to have your B12 level measured.
  • If your level is below target, talk with your provider about treatment options. You may be able to take a daily B12 supplement, for example, rather than receiving B12 injections.
  • Certain medications can affect B12 levels, including proton pump inhibitors, such as omeprazole (Prilose) and lansoprazole (Prevacid) and histamine 2-receptor antagonists, such as cimetidine (Tagamet) and ranitidine (Zantac). Let your provider know if you are taking any of these medications.
  • Because older adults are at risk of a vitamin B12 deficiency, start getting regular blood tests for this when you are in your 60s. Some health experts recommend that older adults take a daily B12 supplement.
  • Eat foods that contain vitamin B12. If you follow a vegetarian or vegan eating pattern, focus on eating foods fortified with vitamin B12 or consider taking a multivitamin.

Want to learn more about metformin? Read “What to Know About Metformin,” “Diabetes Medicine: Metformin,” and “Metformin: The Unauthorized Biography.”

Amy Campbell, MS, RD, LDN, CDCES

Amy Campbell, MS, RD, LDN, CDCES

Amy Campbell, MS, RD, LDN, CDCES on social media

A Registered Dietitian and Certified Diabetes Educator at Good Measures, LLC, where she is a CDE manager for a virtual diabetes program. Campbell is the author of Staying Healthy with Diabetes: Nutrition & Meal Planning, a co-author of 16 Myths of a Diabetic Diet, and has written for  publications including Diabetes Self-Management, Diabetes Spectrum, Clinical Diabetes, the Diabetes Research & Wellness Foundation’s newsletter,, and

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