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Observational studies have suggested that metformin causes vitamin B12 deficiency in some patients; researchers have proposed several possible mechanisms whereby metformin might interfere with B12 absorption. Understanding this interaction is important, because B12 deficiency could exacerbate neuropathic symptoms in patients with diabetes.
In this prospective case-control study, Canadian investigators identified 122 type 2 diabetic patients with peripheral neuropathy: Half had taken metformin for at least 6 months, and half had never received metformin. Otherwise, clinical characteristics of the groups were similar.
Median serum B12 level was significantly lower in the metformin group than in the no-metformin group (231 vs. 486 pmol/L). Metformin recipients also had significantly higher levels of homocysteine and methylmalonic acid (markers of B12 deficiency) and significantly worse scores on standardized clinical assessments of severity of neuropathy. In multivariate analyses controlled for age, duration of diabetes, and glycosylated hemoglobin (HbA1c) level, metformin therapy was associated independently with worse neuropathic symptoms.
Wile DJ and Toth C. Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy. Diabetes Care 2010 Jan; 33:156.
Comment
This study strengthens the case for an effect of metformin therapy on vitamin B12 levels. The analysis also suggests that this interaction worsens neuropathy, but confounding by unknown factors could be responsible for this observation. In one randomized placebo-controlled trial, metformin lowered B12 levels (J Intern Med 2003; 254:455); now, we need a trial to determine whether B12 supplementation is beneficial for diabetic patients who take metformin.