Association of vitamin B12 deficiency with metformin use in patients with type 2 diabetes treated in the largest tertiary care hospital in Qatar

Background: Data on the effect of metformin on serum vitamin B12 (VitB12) level in patients with type 2 diabetes mellitus (T2DM) in Qatar are limited; therefore, we aimed to assess the prevalence of VitB12 deficiency and its related factors among patients with T2DM treated with metformin at Hamad General Hospital in Doha, Qatar, from January 1, 2017, to December 31, 2017. Methods: This cross-sectional analytical study involved patients with T2DM aged $18 years who used metformin for at least 3 months. The serum VitB12 was quantified on a chemiluminescent enzyme immunoassay analyzer using Cobas e 801 module, Roche, and VitB12 deficiency was defined as serum VitB12 level of #145 pmol/L. All data were obtained from the patients' electronic medical records. Results: The study recruited 3124 eligible patients with T2DM. The overall prevalence of metformin- associated VitB12 deficiency was 30.7% [95% confidence of interval, 0.290–0.323]. A significant difference exists in the median VitB12 levels between the VitB12-normal and VitB12-deficient groups [129 vs. 286; p , 0.001]. Compared with the VitB12- normal group, the VitB12-deficient group had higher mean body mass index (BMI) ( p , 0.001) and consumed higher doses of metformin ( p 1⁄4 0.001). They also more often used sulfonylurea ( p 1⁄4 0.004), dipeptidyl peptidase-4 inhibitor ( p , 0.001), thia- zolidinediones ( p , 0.001), glucagon-like peptide 1 [GLP-1] receptor agonists ( p , 0.001), alpha- glucosidase inhibitor ( p , 0.001), and H2 blocker/ proton pump inhibitors [PPI] ( p , 0.001) than the VitB12-normal group. Moreover, the VitB12-normal group consumed more calcium supplements ( p , 0.001) than the VitB12-deficient group. In the multivariate analysis, independent risk factors for metformin-associated VitB12 deficiency in patients with T2DM include high daily dose of metformin .2000 mg, male gender, high BMI, smoking, sulfonylurea, dipeptidyl peptidase-4 inhibitor, H2 blockers/PPI, low fasting blood glucose, and low hemoglobin. Conclusion: This study showed a high prevalence of VitB12 deficiency in patients with T2DM taking metformin and a significant negative correlation between the daily dose of metformin and serum VitB12 level. Therefore, regular screening for serum VitB12 is necessary in patients with T2DM on metformin treatment, especially those who have the abovementioned risk factors.