According to a study published in the Journal of the American Geriatrics Society, long-term metformin use is significantly associated with lower serum vitamin B12 levels, but those at risk often are not monitored for this deficiency.

Researchers conducted a retrospective cohort study to evaluate the association between long-term metformin therapy and monitoring serum vitamin B12 at a single Veterans Affairs Medical Center (VAMC) from 2002–2012. Veterans aged ≥50 years with either type 2 diabetes receiving long-term metformin therapy (n=3,687) or veterans without diabetes and no metformin prescription (n=13,258) were included in the study. 

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Long-term metformin therapy was defined as a prescription for ≥500mg daily for ≥6 consecutive months. The study showed that only 37% of older adults with diabetes receiving metformin were tested for vitamin B12 levels after long-term metformin prescription. The average B12 concentration was significantly lower in the metformin-exposed group vs. those without diabetes (439.2pg/dL vs. 522.4pg/dL; P=0.0015). 

Also, about 7% of patients with diabetes receiving metformin were considered vitamin B12 deficient (<170pg/dL) vs. 3% of patients without diabetes or metformin exposure (P=0.001). 

After adjusting for gender, race, ethnicity, body mass index, and number of years treated at the VAMC, patients using metformin were 2–3 times more likely not to be tested for vitamin B12 status vs. those not exposed to metformin based on their age. 

Since metformin is first-line therapy for treating type 2 diabetes, “clinical decision support should be considered to promote serum B12 monitoring among long-term metformin users for timely identification of the potential need for B12 replacement,” concluded study author Vijaya Kancherla, PhD.

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