Evaluation of Vitamin B12 Monitoring in a Veteran Population on Long-Term, High-Dose Metformin Therapy

BACKGROUND: Mefforrnin 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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 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. CONCLUSIONS: 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 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.