Send to:

Choose Destination
See comment in PubMed Commons below
Ann Pharmacother. 2012 Nov;46(11):1470-6. doi: 10.1345/aph.1R223. Epub 2012 Oct 31.

Evaluation of vitamin B12 monitoring in a veteran population on long-term, high-dose metformin therapy.

Author information

  • 1VA Maryland Healthcare System-Department of Pharmacy, Baltimore, MD.



Metformin can result in vitamin B(12) deficiency, potentially leading to complications such as neuropathy. Annual monitoring of vitamin B(12) has been suggested; however, it is unknown whether current practice reflects this recommendation.


To identify vitamin B(12) monitoring patterns in patients on long-term, high-dose metformin. Secondary objective was to determine the frequency of new vitamin B(12) deficiency, anemia, and neuropathy documented after initiation of high-dose metformin.


Electronic medical records of veterans treated at the Veterans Affairs Maryland Healthcare System with high-dose metformin (≥2000 mg/day) as of November 1, 2010, were reviewed. Data regarding metformin treatment, vitamin B(12) measurements, and documentation of vitamin B(12) deficiency, cyanocobalamin supplementation, anemia, and neuropathy were collected. Subjects treated with metformin for less than 1 year or those with documented peripheral neuropathy, megaloblastic anemia, vitamin B(12) deficiency, or a condition associated with vitamin B(12) malabsorption prior to metformin initiation were excluded.


Subjects (N = 235) had a mean metformin dose of 2050 mg/day and mean duration of treatment of 5.2 years. Sixty percent did not have vitamin B(12) measured. Of subjects receiving metformin for 10 years or more, nearly half (46%) never had vitamin B(12) measured. New documentation of vitamin B(12) deficiency or cyanocobalamin supplementation was found in 5.5% of the population, and anemia was found in 12%. Of the 14% with new neuropathy, 42% did not have vitamin B(12) measured.


Vitamin B(12) was not routinely monitored in patients on high-dose metformin, even in those at highest risk (≥10 years of therapy), or in those with potential manifestations of vitamin B(12) deficiency (neuropathy). Cases of vitamin B(12) deficiency and resulting anemia or neuropathy may be undiagnosed and untreated because of lack of monitoring. Prospective studies examining the effect of increased vitamin B(12) monitoring on identification and treatment of vitamin B(12) deficiency in patients on metformin are warranted.

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Write to the Help Desk