Vitamin B12 Deficiency in Diabetic Patients on Chronic Metformin Therapy

Abstract

Introduction: Since its approval and universal acknowledgement in the 1990's as a first line agent for the treatment of Diabetes Mellitus Type II, studies have shown vitamin B12 deficiency to be a complication of chronic metformin therapy. Despite this awareness and few studies aimed at the general population, a systematic assessment of the prevalence of vitamin B12 deficiency in Type II diabetics on metformin in the veteran population has not been performed. Methods: A retrospective data analysis at a VA Hospital from 2002-2012 was performed which included 3844 diabetic patients on metformin who had B12 levels drawn while on metformin. Vitamin B12 deficiency was defined as B12 ≤ 218 pg/mL and further subdivided into moderate (218-175 pg/mL) and severe (1500 mg/day). The duration of metformin therapy was categorized as short (4 years) and long (>4 years). Results: Overall prevalence of B12 deficiency while on metformin therapy was 9.8 %. Only 38 % of the patients had baseline B12 levels checked prior to their becoming deficient. There was a significant difference when comparing B12 deficiency between control vs. metformin group (P < 0.0001 CI (2.5-10.6), OR 5.1, and Metformin vs. Insulin group P < 0.0001, CI (0.13-1.43), OR 11.6 (Table 1). There was a significant difference between short duration vs. long duration of metformin in regards to moderate vs. severe B12 deficiency (Table 2). In addition, there was a significant difference between low dose metformin group and high dose metformin group in regards to moderate vs. severe B12 deficiency (Table 2).Table 1: P value, Confidence Interval, and OR for Control vs. Metformin vs. Insulin.Table 2: Comparison of Duration and Dosing of Metformin therapy vs. B12 deficiencyConclusion: We report 9.8% overall prevalence of patients with B12 deficiency while on metformin. Compared to insulin-treated diabetics and non-diabetics, metformin group had significantly more patients with overt B12 deficiency (B12 < 218 pg/mL). Higher dose and longer duration appear to worsen the problem. B12 deficiency develops gradually and is frequently overlooked although it is easy to treat if suspected and managed in time. Our study highlights the lack of awareness of this important problem as evidenced by the small percentage of veterans that had undergone prior B12 testing (38%). Primary care providers and specialists need to be cognizant of the necessity of Vitamin B12 testing with chronic metformin therapy.