Vitamin B12 Deficiency in Patients Receiving Metformin: Clinical Data

We read with interest the excellent article by Ting and colleagues¹ about risk factors of vitamin B₁₂ deficiency in patients receiving metformin. We would like to offer some findings from our own experience. To date, more than 30 patients with metformin-associated vitamin B₁₂ deficiency have been registered in a cohort study of cobalamin deficiency in the University Hospital of Strasbourg, Strasbourg, France (partial data were previously published²). An analysis of these patients (median age, 66 years) proves some of the comments by Ting et al.¹ First, the clinical severity of metformin-associated vitamin B₁₂ deficiency is moderate, with 90% of minor hematological abnormalities (median hemoglobin levels and mean erythrocyte cell volume, 11.5 g/dL and 95.4 fL, respectively) and 30% of mild peripheral sensitive neuropathy. However, there were 2 cases (5.7%) of symptomatic anemia and pancytopenia (requiring transfusions). The mean ± SD serum vitamin B₁₂ and total homocysteine levels were 156 ± 31 pg/mL (range, 87-200 pg/mL) (115.1 ± 22.9 pmol/L [range, 64-148 pmol/L) and 2.0 ± 0.8 mg/L (range, 2-3 mg/L) (14.8 ± 5.7 μmol/L [range, 13-22 μmol/L]). Second, an analysis of our cases suggests that the principal mechanism of vitamin B₁₂ deficiency in patients receiving metformin is undoubtedly food-cobalamin malabsorption. In fact, of 34 patients' responses to the diagnostic criteria we had previously published,³ 1 patient had a malabsorption with chronic diarrhea.² In our opinion, this mechanism of food-cobalamin malabsorption may explain the constant efficacy of oral crystalline cyanocobalamin therapy that we have observed as a benefit of calcium supplementation. To our knowledge, discontinuation of metformin therapy remains controversial, but our results suggest that it may be unnecessary.