Vitamin B12 Deficiency Associated With Concomitant Metformin and Proton Pump Inhibitor Use

M etformin and proton pump in-hibitors have been implicated in decreasing levels of vitamin B 12 independently. The purpose of this study was to evaluate the effect of concomitant use of metformin and proton pump inhibitors on the incidence of vitamin B 12 deficiency. A retrospective chart review was done using the computerized patient record system at the Memphis VA Medical Center for 614 patients with type 2 diabetes and previously collected vitamin B 12 levels. Patients were excluded if they were over the age of 60 years; on a vegetarian diet; had been diagnosed with pernicious anemia, documented by a positive Schilling test or anti-intrinsic factor antibody, or pancreatic exocrine insufficiency; had undergone a gastrectomy or bowel resection; or had been treated with supplemental calcium, H2 blocker, or B 12 within 3 months of data collection. The vitamin B 12 levels were assessed using a competitive immu-noassay with direct chemiluminescent technology. Deficiency was defined as vitamin B 12 levels ,300 pg/mL. A x 2 test was used to compare patients taking metformin or proton pump inhibitors alone and those taking both with a control population taking neither medication. Mean 6 SD age was 65.08 6 9.23 years, with a majority of male patients (96.3%). African Americans comprised 40.07% of the study population and Caucasians 50.33%; 9.6% had " other " listed for race. The incidence of vitamin B 12 deficiency was found in 48 (22.2%) of the 216 control subjects. This was not significantly different compared with 32 (21.91%) of the 146 metformin subjects or 33 (25.58%) of the 129 proton pump in-hibitor alone subjects (P 5 0.9454 and 0.4763). However, there was a significant difference found in 42 (34.15%) of the 123 concomitant metformin and proton pump inhibitor subjects compared with the control group (P 5 0.0096). Metformin is a first-line medication used in the treatment of type 2 diabetes but has also been shown in multiple studies to reduce serum B 12 levels in 10–30% of patients (1). Proton pump inhibitors are also commonly used medications for the treatment of gastroesophageal reflux disease and peptic ulcer prevention and treatment and, short-term, have been shown to decrease B 12 levels from 3.4 to 0.4% (P , 0.05) in a 2-week period (2). However, studies looking at long-term proton pump inhibitor use and vitamin B 12 deficiency have yielded conflicting results (3,4). Ting et al. (5) found no significantly …