Objective : Vitamin B12 is a water-soluble vitamin of animal origin and is required for proper red blood cells formation, neurological function, and DNA synthesis. Metformin is postulated to reduce the absorption of vitamin B12.
Methods : In this observational study, 817 subjects with type 2 diabetes for minimum of 3 years were screened (so that effect of diabetes and associated dietary changes on vitamin B12 level can be factored in). Patients with history of vitamin B12 use, PPI/H2blocker use in last 2 years, type 1 diabetes, CKD stage ≥4, chronic liver disease, alcohol abuse, pernicious anaemia, autoimmune disorders, celiac disease, pregnancy, tropical sprue or any gastro intestinal surgery, were excluded. Total 173 subjects were enrolled: 117 in metformin group and 56 in non-metformin group. Only those were enrolled in metformin group who were taking metformin for more than 2 years, as it take 2-3 years in normal person to deplete hepatic store of vitamin B12. Metformin group was further subdivided in three subgroups depending upon metformin dosage: metformin 1000mg/d, metformin 1700mg/d and metformin ≥ 2000mg/d.
Metformin group had significantly lower mean vitamin B12 values (290.01±239.14 pg/ml) compared to non-metformin group (403.37±87.64 pg/ml, p value=0.002). In ≥2000mg/d metformin group 79%, in 1700mg/d metformin group 66%, and in 1000mg/d metformin group 29.7%, had vitamin B12 deficiency (p value<.0001).
Mean vitamin B12 levels was 351.17 pg/ml in patients taking metformin 1000mg/d, 181.0 pg/ml in metformin 1700mg/d group and 189.51 pg/ml in metformin 2000mg/d group. Mean vitamin B12 levels were lower in patient receiving metformin for > 3 years as compared to those receiving metformin for < 3 years (263.10 pg/ml vs. 384.18 pg/ml, p value = .002).
Discussion : Various studies reports prevalence of vitamin B12 deficiency ranging from 33% to 67% in general Indian population. In western studies vitamin B12 deficiency in metformin users varied from 5.8% to 22% but in current study, 40.6% in metformin group had serum vitamin B12 levels <211 pg/ml compared to 12.5% amongst non-metformin group, suggesting Indians are at much higher risk of developing vitamin b12 deficency probably because of their peculiar dietary habits.
Conclusion : In the present study, vitamin B12 levels were significantly lower in metformin group as compared to non-metformin group. This effect of metformin depends on dosage as well as duration of metformin use. This calls for monitoring of vitamin B12 levels particularly in patients on higher dosage (> 1700mg/d) and if duration of treatment is longer than three years, with timely supplementation if required.
SN Medical College, Jodhpur, India
Jodhpur, Rajasthan, India
Consultant Diabetologist Physician & Professor of Medicine
Nagaur, Rajasthan, India
Practicing medicine in a goverment hospital