Greater Glasgow and Clyde Medicines

Metformin and reduced vitamin B12 levels

Key messages

  • Metformin can commonly reduce vitamin B12 levels in patients, which may lead to vitamin B12 deficiency. Refer to MHRA Drug Safety Update here.

  • B12 deficiency risk increases with higher metformin doses, longer treatment duration and patients with a risk of B12 deficiency (see below for additional risk factors)

  • Patients with a vitamin B12 deficiency can be asymptomatic or they can present with symptoms of megaloblastic anaemia or neuropathy or both (see below for other symptoms). If B12 deficiency is suspected, take blood levels. Consider periodic monitoring in patients prescribed metformin and with risk factors (see below).

  • There is no need to discontinue metformin due to B12 deficiency. If B12 deficiency is confirmed, follow the NHSGGC guideline on the treatment of B12 deficiency in adults. B12 replacement is only required for patients on metformin if B12 deficiency anaemia or neuropathy is suspected.

  • It is important to inform patients of the potential side effects when initiating metformin therapy, and alert them to the symptoms associated with B12 deficiency

  • Report any suspected adverse drug reactions with metformin on a Yellow Card

    Yellow Card | Making medicines and medical devices safer (mhra.gov.uk)

 

The mechanism for B12 deficiency in patients on metformin is currently thought to be multifactorial, comprising of altered intestinal motility, bacterial overgrowth, and reduced uptake of vitamin B12 within the small intestine.


Patients who are at risk of B12 deficiency include:

  • Patients with a condition associated with reduced vitamin B12 absorption (such as elderly people, and those with gastrointestinal disorders such as total or partial gastrectomy, Crohn’s disease and other bowel inflammatory disorders, or autoimmune conditions)

  • Patients with a diet deficient in vitamin B12 (such as strict vegan and some vegetarian diets)

  • Patients prescribed concomitant medication known to impair vitamin B12 absorption (including proton pump inhibitors, H2 blockers, hormonal preparations, anticonvulsants and colchicine)

  • Patients with a genetic predisposition to vitamin B12 deficiency, such as intrinsic factor receptor deficiency (Imerslund-Gräsbeck syndrome) and transcobalamin II deficiency

  • Patients where a previous baseline vitamin B12 level was at the lower end of the normal range

 

Symptoms of B12 deficiency

Symptoms can vary and usually develop gradually, but can worsen if left untreated. Patients should be advised to seek medical advice if they develop:

  • New or worsening symptoms of extreme tiredness

  • A sore and red tongue

  • Pins and needles

  • Pale or yellow skin

Other symptoms of B12 deficiency include:

  • Mental disturbance (depression, irritability, cognitive impairment)

  • Mouth ulcers

  • Visual and motor disturbances

 

Further information on the treatment of vitamin B12 deficiency in adults can be found in the following blogs:

 

Published: 14/11/2022. Medicines Update blogs are correct at the time of publishing.