B12 Deficiency 'Should Be Tested in Metformin Patients'

Liam Davenport

November 22, 2018

Diabetes patients taking metformin should have their vitamin B12 levels assessed regularly to avoid peripheral nerve damage, say UK researchers after finding that the vast majority of patients are not tested and almost 1 in 10 have vitamin B12 deficiency.

While metformin is recommended for the first-line treatment of type 2 diabetes, it is associated with vitamin B12 deficiency, which itself increases the risk of peripheral neuropathy.

Not a Very Well-known Side Effect

In their study of more than 150 women with diabetes presented at the Society for Endocrinology BES 2018 conference in Glasgow, the researchers showed that 64% had not been tested for vitamin B12 deficiency.

Moreover, almost 10% of patients were found to have vitamin B12 deficiency, although only just over 6% were being treated.

Dr Kaenat Mulla, Nottingham University Hospitals, Nottingham, who led the study, told Medscape News UK that she believes vitamin B12 deficiency is not tested more widely because "it's not a very well-known side effect".

"It's only if you're an endocrinologist you will know about it," she said, pointing out that, if a patient with diabetes develops nerve damage it gets "attributed to the fact that they have diabetes".

Currently, there are no official guidelines on the screening for vitamin B12 levels in patients treated with metformin, although the British Society of Haematology recommends that levels are checked if there is a strong clinical suspicion of deficiency.

Extra B12 Checks

Dr Mulla would, however, like to see diabetes patients taking metformin to be checked for vitamin B12 deficiency more often, and this to be enshrined in updates to the guidelines.

"We need to ensure deficiencies are adequately treated to avoid irreversible nerve damage," she commented in a news release.

She emphasised, however, that "metformin remains the best treatment for type 2 diabetes" and that their findings "should not discourage patients from taking it, but encourage doctors to monitor vitamin B12 levels more routinely, so any deficiency can quickly be treated".

Ideally, Dr Mulla would like to see patients taking metformin tested for vitamin B12 before starting treatment, as well as during follow-up.

She told Medscape News UK that there had been several strands of research presented at the conference showing that being vitamin B12 deficient prior to having diabetes "affects adipose tissue and puts them at higher risk of insulin resistance".

She added: "If we put them on metformin and that makes them more deficient, we're not really winning."

Study Details

For the first part of the study, the researchers conducted a review of patients registered at a single general practice in Nottingham who had a diagnosis of type 2 diabetes and were taking metformin therapy.

They chose to include all women who were prescribed the drug either as 500 mg tablets or 500 mg modified release tablets, which yielded a total of 157 patients available for analysis.

Dr Mulla explained that there was "no particular reason" for why they decided to focus on solely female patients, but did so to "simplify" the study and because it was "easier to pick either/or".

The average age of the women was 63.4 years.

The most common dose of metformin was 2000 mg per day, and the average duration of drug use was 6.4 years. Sixty per cent of patients were on the highest metformin dose, and had been taking it for an average of 6.6 years.

The researchers found that 64% of the patients had not had their vitamin B12 levels tested. In addition, 6.4% had already been diagnosed with vitamin B12 deficiency and were given replacement injections.

For the next phase of the study, they sent letters and blood forms to patients to invite them for blood tests to determine their full blood count and levels of vitamin B12 and intrinsic factor.

Patients who had their annual check within the next month had the tests included in the next follow-up.


The team found that 72.2% of patients were compliant with the blood tests. These revealed that five additional patients had vitamin B12 deficiency, of whom three also had anaemia.

It was therefore calculated that, by combining the results from phase one and two of the study, 9.6% of the women had vitamin B12 deficiency.

Based on their results, practice has already changed at the medical centre, with all diabetes patients having their vitamin B12 levels assessed as part of their annual check-up.

However, Faye Riley, research communications officer at Diabetes UK, commented to Medscape News UK via email: "It is important for doctors to be aware of the link between metformin and an increased risk of vitamin B12 deficiency. However, prior research has concluded that routine testing for B12 levels wouldn’t be cost-effective or clinically useful for people using this medication. 

"This particular study is limited to observations from one medical center, so at the moment there isn't enough evidence to suggest a review of current guidelines is needed."

The researchers now plan to extend their audit to strengthen their findings in a larger cohort.

No funding or conflicts of interest declared.

Society for Endocrinology BES 2018: Abstract P092. Presented 21 November.

Endocrine Abstracts (2018) 59 P092 DOI: 10.1530/endoabs.59.P092

Editor's Note: This article was updated to include comment fro Diabetes UK.


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