An observational study of the effect of metformin on B12 status and peripheral neuropathy

Abstract

Aims Metformin is associated with lowering of vitamin B12 levels. We hypothesise that holotranscobalamin (holoTC) and methylmalonic acid (MMA) are more sensitive indicators of B12 deficiency in patients receiving metformin therapy, and that these correlate with declining peripheral neurological function. Methods Patients with type 2 diabetes were recruited and divided into those receiving metformin for greater than 6 months and a non-metformin group. Baseline characteristics were measured in both groups including vitamin B12, holoTC and MMA concentrations. Neurological function was assessed using neurothesiometry, monofilament, Neuropathy Total Symptom Score-6 questionnaire and the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire. Results In total, 202 patients were recruited: 152 in the metformin group and 50 in the non-metformin group. Vitamin B12 levels were lower in the metformin group (219.1±105.4 ng/L, 281.4±95.1 ng/L, p<0.001). HoloTC was significantly lower in the metformin group (54.8±30.5 pmol/L, 70.1±26.0 pmol/L, p=0.002). No significant difference in serum MMA was observed between the two groups (0.40±0.26 μmol/L, 0.35±0.22, p=0.23). No significant difference in neurological function was observed between the groups. Conclusion Although metformin therapy is associated with lower vitamin B12 status there does not appear to be any significant effect on peripheral neuropathy in those receiving metformin. We do not recommend changing current practice to routinely monitor or replace patients receiving metformin with vitamin B12 unless clinically indicated.