Metformin and vitamin B12: why deficiency can develop and which symptoms are typical

One tablet with breakfast, one with dinner – for many people with type 2 diabetes, metformin is as much a part of daily life as brushing their teeth. Hardly anyone thinks about vitamin B12 at the same time. Have you ever wondered whether your medication slowly changes something in your nutrient balance?

Metformin and vitamin B12: what happens in the body

Metformin has been one of the most widely used diabetes medications for decades. It mainly reduces glucose production in the liver and improves the action of insulin. But it also acts in the gut – exactly where vitamin B12 is absorbed.

The route vitamin B12 takes into the body is unusually long: it is released from food in the stomach, binds to intrinsic factor and is only absorbed in the last section of the small intestine, the ileum. For this final step, the gut cell needs calcium. A widely discussed explanation is that metformin interferes with this calcium-dependent uptake. Changes in gut motility and gut flora are also discussed as contributing factors. The mechanism is not fully settled – but the observation itself is well documented.

Vitamin B12 deficiency caused by metformin: what studies show

A meta-analysis found that metformin measurably lowers vitamin B12 levels after just six weeks to three months – by about 57 pmol/l on average (PubMed 27130885). For some people this is enough to slip into borderline or true deficiency. Another meta-analysis of 31 studies confirmed a roughly twofold risk of vitamin B12 deficiency with metformin; the effect depended on dose and duration (PubMed 30615306).

The long-term follow-up of the US Diabetes Prevention Program is particularly revealing: after about five years, 19.1 percent of participants in the metformin group had low or borderline-low B12 levels, compared with 9.5 percent in the placebo group. Each additional year of use increased the risk further (PubMed 26900641).

To put this in perspective: metformin is a proven and well-studied medication. The question is not whether it should be taken – that is your doctor's decision – but whether B12 status is being kept in view. Do not stop a prescribed medication without talking to your doctor first.

Metformin and vitamin B12 deficiency: symptoms worth knowing

Vitamin B12 deficiency usually develops slowly because the body keeps stores in the liver. The textbook signs mainly affect the blood and nerves (PubMed 23301732):

• tingling, numbness or burning in the feet and hands
• unsteadiness when walking, especially in the dark
• persistent tiredness and reduced stamina, for example due to anaemia
• problems with concentration and memory
• a smooth, red or burning tongue

This is a real difficulty: tingling and numbness in the feet are also typical of diabetic nerve damage. A review describes that B12 deficiency on metformin can cause or accelerate such neuropathy (PubMed 35491956). Because the complaints are similar, the two are hard to tell apart without a measurement. None of these signs proves a deficiency. New or worsening symptoms should therefore be checked by a doctor.

Who is particularly affected

According to these studies, the likelihood of low B12 levels increases with, among other things:

• longer use and higher daily doses (PubMed 30615306)
• older age, because stomach acid and thus B12 release often decline (PubMed 23301732)
• simultaneous use of acid blockers such as proton pump inhibitors (PubMed 35491956)
• vegetarian or vegan diets, because B12 is found almost only in animal foods
• after stomach or bowel surgery, for example bariatric surgery (PubMed 35491956)

Measure instead of guessing: checking your vitamin B12 status

Because the symptoms are so unspecific, a blood test is the more reliable route. The authors of the 2016 meta-analysis consider it sensible to monitor B12 status in people taking metformin (PubMed 27130885). A review recommends periodic checks, especially after more than five years of use, when liver B12 stores may be depleted (PubMed 35491956).

With the Vitamin Check Basic you can have vitamin B12 measured together with folic acid, vitamin D3, vitamin E and coenzyme Q10 from a few drops of capillary blood – collected comfortably at home and analysed in the partner laboratory. Good to know: a total B12 value in the lower normal range is not always conclusive (more on this in Always tired, but your blood tests are fine?). Depending on the result, professionals may suggest additional markers such as methylmalonic acid, homocysteine or holotranscobalamin, which can show a deficiency earlier and more accurately (PubMed 23301732) (PubMed 35491956).

Taking metformin and vitamin B12 together? What to discuss with professionals

This question comes up very often in search engines. The reviews cited here do not describe a known interaction that speaks against taking them at the same time. Whether you need a supplement at all, in what form and for how long, depends on your measured value, your symptoms and your other medications. That belongs in a conversation with professionals – not in a self-experiment.

• When was my vitamin B12 last measured, and what was the value?
• Do my symptoms fit diabetic nerve damage, B12 deficiency, or both?
• Would an additional marker such as holotranscobalamin or methylmalonic acid be useful for me?
• How often should I have the value checked at my dose and duration of use?

The ORY expert team is also available to discuss your results with you.

In brief

• Long-term metformin use can lower vitamin B12 levels; this is documented in several meta-analyses.
• The risk rises with dose, duration of use and age.
• Typical signs of deficiency affect nerves and blood – and resemble diabetic neuropathy.
• A blood test provides clarity; a medication is never stopped on your own.

Frequently asked questions

Does metformin cause vitamin B12 deficiency?

Not in everyone, but considerably more often than without metformin. Meta-analyses show a roughly twofold risk of vitamin B12 deficiency and measurably lower levels, depending on dose and duration (PubMed 30615306).

Why does metformin cause vitamin B12 deficiency?

The main hypothesis is that metformin impairs the calcium-dependent absorption of vitamin B12 in the ileum. Changes in gut flora and gut motility are also considered contributing factors. The exact mechanism is not yet fully understood.

What are the symptoms of vitamin B12 deficiency caused by metformin?

Textbook signs include tingling or numbness in the feet and hands, unsteady gait, tiredness due to anaemia, concentration problems and a red tongue (PubMed 23301732). These signs are unspecific and should be checked by a doctor.

Can you take metformin and vitamin B12 together?

The reviews cited do not describe an interaction that speaks against it. Whether and how to supplement vitamin B12 is best discussed on the basis of a measured value with your doctor or the ORY expert team.

Is vitamin B12 deficiency a side effect of metformin?

Yes, falling vitamin B12 levels are a known side effect of long-term metformin use. Unlike digestive complaints, which often appear at the start and then ease, it usually becomes noticeable only after months or years – and often without clear signs. That is why a measurement reveals more than how you feel (PubMed 26900641).

How often should vitamin B12 be checked on metformin?

There is no fixed schedule for everyone. Because the risk rises with each year of use (PubMed 26900641), regular checks are a sensible topic to raise if you have taken it for a long time, are older or have symptoms.

Should I stop metformin if my B12 is low?

No, not on your own. Do not stop a prescribed medication without talking to your doctor first. A low B12 level can usually be treated specifically without calling the diabetes therapy into question.

Sources

1. Chapman LE, Darling AL, Brown JE. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes: A systematic review and meta-analysis. Diabetes Metab. 2016;42(5):316–327. PubMed 27130885
2. Yang W, Cai X, Wu H, Ji L. Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. J Diabetes. 2019;11(9):729–743. PubMed 30615306
3. Aroda VR et al.; Diabetes Prevention Program Research Group. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754–1761. PubMed 26900641
4. Stabler SP. Clinical practice. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149–160. PubMed 23301732
5. Bell DSH. Metformin-induced vitamin B12 deficiency can cause or worsen distal symmetrical, autonomic and cardiac neuropathy in the patient with diabetes. Diabetes Obes Metab. 2022;24(8):1423–1428. PubMed 35491956