Metformin and reduced vitamin B12 levels: new advice for monitoring patients at risk

A warning was issued in June 2022 by the Medicines and Healthcare products Regulatory Agency (MHRA) about metformin. It says:

“Decreased vitamin B12 levels, or vitamin B12 deficiency, is now considered to be a common side effect in patients on metformin treatment, especially in those receiving a higher dose or longer treatment duration and in those with existing risk factors. We are therefore advising checking vitamin B12 serum levels in patients being treated with metformin who have symptoms suggestive of vitamin B12 deficiency. We also advise that periodic monitoring for patients with risk factors for vitamin B12 deficiency should be considered.”

The known adverse drug reaction of vitamin B12 deficiency was recently reviewed after which, the MHRA agreed that the product information for medicines containing metformin should be updated to state that vitamin B12 deficiency is a common adverse drug reaction, and may affect up to 1 in 10 people who take it. It has also been updated to note that the risk of this adverse reaction occurring increases with increasing metformin dose, with treatment duration and in patients with risk factors known to cause vitamin B12 deficiency.

The advice for patients and carers:

• if you are taking metformin, seek medical advice if you develop new or worsening symptoms of extreme tiredness, a sore and red tongue, pins and needles, or pale or yellow skin – these can be signs of low vitamin B12 levels,
• other symptoms may include mental disturbance (depression, irritability, cognitive impairment), glossitis (swollen and inflamed tongue), mouth ulcers, and visual and motor disturbances or it can be asymptomatic,
• it is important for patients with anaemia or neuropathy caused by vitamin B12 deficiency to be diagnosed and treated as soon as possible to avoid the development of permanent symptoms,
• you may need blood tests to find out the cause of your symptoms; these symptoms can also be caused by diabetes or other unrelated health issues,
• you can keep taking metformin while vitamin B12 levels are being corrected,
• do not stop your treatment without first discussing this with your doctor.

About metformin and vitamin B12 deficiency
Metformin is a medicine authorised to treat Type 2 diabetes mellitus, to help prevent Type 2 diabetes in patients at high risk of developing it and sometimes as an addition for Type 1 diabetes treatment.

Vitamin B12 is a nutrient that helps to keep the body’s nerve and blood cells healthy. It is found in foods of animal origin including milk, cheese, yoghurt, and eggs. It is also added to some fortified foods such as breakfast cereals. Common causes of vitamin B12 deficiency include infections, malabsorption, medical conditions (Crohn’s disease, pernicious anaemia), gastric resection, and inadequate dietary intake.

The risk factors for vitamin B12 deficiency include:

• baseline vitamin B12 levels at the lower end of the normal range,
• conditions associated with reduced vitamin B12 absorption, such as elderly people, those with gastrointestinal disorders such as total or partial gastrectomy, Crohn’s disease and other bowel inflammatory disorders, or autoimmune conditions.
• diets with reduced sources of vitamin B12, such as strict vegan and some vegetarian diets,
• concomitant medication known to impair vitamin B12 absorption including proton pump inhibitors or colchicine,
• genetic predisposition to vitamin B12 deficiency, such as intrinsic factor receptor deficiency.