This site is intended for healthcare professionals

Go to /sign-in page

You can view 5 more pages before signing in

Metformin and vitamin B12 deficiency

Authoring team

Studies have screened outpatients taking biguanides (metformin, phenformin) for B12 deficiency.

  • Thirty per cent of 46 patients undergoing biguanide therapy developed B12 malabsorption, which resolved in half on stopping the drug , however it is unwise to assume that malabsorption of vitamin B12 during biguanide therapy will invariably remit on drug withdrawal; whether persistent malabsorption is due to spontaneous failure or intrinsic factor secretion, or to a permanent effect of the drug is a matter of further study (1).

Mechanism for B12 deficiency in diabetic patients on biguanide therapy (2)

  • People with diabetes may have slow intestinal transit causing bacterial overgrowth and B12 malabsorption
    • however, metformin does not alter oral-caecal transit time
    • no evidence of bacterial overgrowth related to metformin in a controlled trial (2)
  • The B12-intrinsic factor complex uptake by ileal cell membrane receptors is known to be calcium-dependent, and metformin affects calcium-dependent membrane action
    • the resulting B12 deficiency can be reversed by administering calcium, and this seems to be the clearest mechanism (2)

Meformin and anaemia (3):

  • a study evaluated the association between metformin use and anemia risk in type 2 diabetes, and the time-course for this, in a randomized controlled trial (RCT) and real-world population data (3)
  • the study examined data from two RCTs and real-world population data
    • anemia was defined as a hemoglobin measure of <11 g/dL
      • in the RCTs A Diabetes Outcome Progression Trial (ADOPT; n=3,967) and UK Prospective Diabetes Study (UKPDS; n=1,473), logistic regression was used to model anemia risk and nonlinear mixed models for change in hematological parameters
      • in the observational Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) population (n=3,485), discrete-time failure analysis was used to model the effect of cumulative metformin exposure on anemia risk
    • ADOPT, compared with sulfonylureas, the odds ratio (OR) (95% CI) for anemia was 1.93 (1.10, 3.38) for metformin and 4.18 (2.50, 7.00) for thiazolidinediones
      • in ADOPT, hemoglobin and hematocrit dropped after metformin initiation by 6 months, with no further decrease after 3 years.
    • in UKPDS, compared with diet, the OR (95% CI) was 3.40 (1.98, 5.83) for metformin, 0.96 (0.57, 1.62) for sulfonylureas, and 1.08 (0.62, 1.87) for insulin
      • in UKPDS, hemoglobin fell by 3 years in the metformin group compared with other treatments
      • at years 6 and 9, hemoglobin was reduced in all treatment groups, with no greater difference seen in the metformin group
    • in GoDARTS, each 1 g/day of metformin use was associated with a 2% higher annual risk of anemia
      • in the GoDARTS study, of those who developed anemia in the metformin exposed group compared with the non metformin- exposed group, microcytic anemia was more frequent (12.1% vs. 7.3%) and macrocytic less frequent (7.6% vs. 12.3%), suggesting that the
        anemia is not caused by a B12 deficiency
  • the study concluded that "Metformin use is associated with early risk of anemia in individuals with type 2 diabetes, a finding consistent across two RCTs and replicated in one real-world study. The mechanism for this early fall in hemoglobin is uncertain, but given the time course, is unlikely to be due to vitamin B12 deficiency alone"
    • seems unlikely that the mechanism for these early changes in Hb is secondary to B12 deficiency, because individuals should have enough B12 stored to last for between 2 and 5 years
    • main limitation of the reported studies is the lack of B12 measurement and lack of other data to help point to a mechanism mediating the early reduction in Hb caused by metformin treatment

Reference:


Create an account to add page annotations

Annotations allow you to add information to this page that would be handy to have on hand during a consultation. E.g. a website or number. This information will always show when you visit this page.

The content herein is provided for informational purposes and does not replace the need to apply professional clinical judgement when diagnosing or treating any medical condition. A licensed medical practitioner should be consulted for diagnosis and treatment of any and all medical conditions.

Connect

Copyright 2024 Oxbridge Solutions Limited, a subsidiary of OmniaMed Communications Limited. All rights reserved. Any distribution or duplication of the information contained herein is strictly prohibited. Oxbridge Solutions receives funding from advertising but maintains editorial independence.