Methylmalonic acid as an indicator of vitamin B12 deficiency in patients on metformin

Context: Metformin is frequently prescribed for the treatment of type 2 diabetes mellitus. It is recommended as a first line agent by the American Diabetes Association. Vitamin B12 deficiency has been suggested as a side effect of metformin therapy; however, previous studies have not assessed the utility of methylmalonic acid levels as an indicator of vitamin B12 status. Objective: To investigate the prevalence of vitamin B12 deficiency in patients on metformin therapy for diabetes by utilizing both vitamin B12 and methylmalonic acid levels. Design, Setting, and Patients: Eighty-eight patients with diabetes, who were either on or off metformin therapy for at least thirty days, were enrolled in a case-controlled study. Blood work and questionnaires were used for analysis. Main Outcome Measures Study: Aims were to detect a clinically significant difference in the prevalence of vitamin B12 deficiency between metformin users and non-users, where such deficiency is defined by both low vitamin B12 and elevated methylmalonic acid levels. Results: Two Sample Equal Variance T-Tests were used to compare averages of measured values and the Chisquare test was used to determine the significance of calculated vitamin B12 deficiency rates between the two groups of patients. Two separate methods for defining vitamin B12 deficiency were utilized. There was no difference in the prevalence of vitamin B12 deficiency in metformin users compared with non-users by either method. Average homocysteine levels were higher in those not on metformin therapy. Conclusion: Vitamin B12 deficiency as defined by an elevated methylmalonic acid level was no greater in patients with diabetes on metformin therapy versus those patients not on metformin treatment.