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Metformin Use Increases Vitamin B12 Deficiency

Posted: Thursday, October 19, 2006

Results indicate an increased risk of vitamin B12 deficiency associated with current dose and duration of metformin.

A nested case-control study identified risk factors for vitamin B12 deficiency in patients with diabetes treated with metformin.

"Identification of risk factors for metformin-related vitamin B12 deficiency has major potential implications regarding the management of diabetes mellitus," write Rose Zhao-Wei Ting, MBBS, from Prince of Wales Hospital. "First, there is likely to be an improved yield of detecting vitamin B12 deficiency if high-risk individuals can be identified. Second, subjects identified as having substantial risk for metformin-related vitamin B12 deficiency might benefit from empirical screening or primary prevention with other means such as calcium supplementation."

The source population for this nested case-control study was a database that consisted of subjects who had levels of both serum vitamin B12 and hemoglobin A1c and were checked in a central laboratory. The investigators identified 155 cases of diabetes mellitus and vitamin B12 deficiency secondary to metformin treatment, as well as 310 controls who did not have vitamin B12 deficiency while taking metformin.

After adjustment for confounders, there were clinically important and statistically significant associations of vitamin B12 deficiency with dose and duration of metformin use. Each 1-g/day increment in metformin dose conferred an odds ratio of 2.88 (95% confidence interval [CI], 2.15 - 3.87) of developing vitamin B12 deficiency (P < .001).

"Our results indicate an increased risk of vitamin B12 deficiency associated with current dose and duration of metformin use despite adjustment for many potential confounders," the authors write. "The risk factors identified have implications for planning screening or prevention strategies in metformin-treated patients."

"We believe our findings should reinforce the heightened vigilance about vitamin B12 deficiency," the authors conclude. "Enough concerns exist to call attention to the value of vitamin B12 screening, particularly among at-risk patients receiving metformin. Our data underscore the need for monitoring subjects undergoing high-dose and/or prolonged-course metformin therapy."

Source: Diabetes In Control: Arch Intern Med. 2006;166:1975-1979