Association of B12 deficiency and clinical neuropathy with metformin use in type 2 diabetes patients

Abstract

Long-term metformin use has been hypothesized to cause B12 deficiency and neuropathy in Type 2 diabetes patients. However, there is a paucity of Indian data regarding the same. To compare the prevalence of B12 deficiency and peripheral neuropathy in patients with Type 2 diabetes mellitus treated with or without metformin. We recruited patients with Type 2 diabetes and divided them into metformin exposed and nonmetformin exposed groups. We measured baseline demographic variables like age, sex, vegetarian status, and HbA1c levels in both groups. We compared vitamin B12 levels and severity of peripheral neuropathy (using Toronto Clinical Scoring System (TCSS)) in both groups. Definite B12 deficiency was defined as B12 <150 pg/ml and possible B12 deficiency as <220 pg/ml. The difference in vitamin B12 levels and TCSS was calculated in both groups using independent samples t-test. Spearman's rank correlation between cumulative metformin use and B12 level was calculated. Odds ratio of vitamin B12 deficiency in metformin exposed group was also estimated. Mean serum B12 levels was significantly lower in metformin exposed group (n=84) compared with nonmetformin exposed group (n=52) (410±230.7 versus 549.2±244.7, P=0.0011). Mean neuropathy score was significantly higher in metformin exposed group. (5.72±2.04 versus 4.62±2.12, P=0.0064). Odds ratio for possible B12 deficiency was 4.45 (95% CI 1.24-15.97). There was significant negative correlation between cumulative metformin dose and vitamin B12 level (r=-0.68, P<0.0001). Metformin use is associated with vitamin B12 deficiency and clinical neuropathy in Type 2 diabetes patients.