Assessment of serum vitamin B levels and chronic haemato-toxicologic adverse profile induced by metformin pharmacotherapy among type 2 diabetic patients: A prospective analytical study

Background: The potential effect of chronic metformin pharmacotherapy to cause vitamin B 12 deficiency has been of tremendous concern especially among diabetic patients. Haematological abnormalities following vitamin B 12 deficiency among diabetic patients contribute immensely to morbidity and mortality in this group of patients. Aim: This study was designed to elucidate the chronic haemato-toxicologic adverse profile for metformin with respect to its potential to induce vitamin B 12 deficiency via reduction in the gastrointestinal absorption of vitamin B 12 by performing comparative analyses between the serum vitamin B 12 levels and haematological indices among metformin-treated and metformin-naive type 2 diabetes mellitus (DM) patients attending the outpatient Endocrinology Clinic of Irrua Specialist Teaching Hospital (ISTH), Irrua, Edo State, Nigeria, with the rational purpose of alleviating the associated morbidity and mortality. Materials and Methods: This was a case–control, prospective, analytical, and observational study of 200 adult participants (100 per group) attending the Endocrinology Outpatients Clinic of ISTH. Serum vitamin B 12 levels were analysed using an immunoassay technique. Haematological indices were determined using standard methods, and patients examined for clinical features of anaemia. Data were presented using tables and charts. χ 2 and t -tests were used to compare discrete and continuous data, respectively. The receiver operating characteristic (ROC) curve was plotted graphically to determine the sensitivity and specificity of using serum vitamin B 12 assay as a screening and diagnostic test for the haematologic abnormality of ovalocytosis among the metformin-treated type 2 DM patients. Results: A total of 200 type 2 diabetic patients comprising 100 metformin-treated and 100 metformin-naive patients with average age of 55.8 ± 9.3 years were studied. The mean serum vitamin B 12 levels in metformin-treated and metformin-naive participants with frank vitamin B 12 deficiency (i.e. mean serum vitamin B 12 level ≤ 199 pg ml −1 ) were 158.29 ± 29.27 pg ml −1 and 173.95 ± 14.21 pg ml −1 , respectively ( p = 0.028). This was significantly lower for the metformin-treated group compared to metformin-naive group with respect to the participants with frank vitamin B 12 deficiency. There were instances of statistically significant differences between the mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and total white blood cell (WBC) count among the metformin-treated compared to the metformin-naive type 2 DM patients. The ROC curve showed that serum vitamin B 12 assay had moderate sensitivity of 72% with moderate specificity of 66% at detecting the presence and absence of ovalocytosis in the presence and absence of frank vitamin B 12 deficiency, respectively, among the metformin-treated group (i.e. serum vitamin B 12 ≤ 199 pg ml −1 with p = 0.002). Conclusion: The occurrence of vitamin B 12 deficiency was high among metformin-treated type 2 DM patients. Our study showed remarkable statistically and clinically significant differences in the chronic haemato-toxicology of metformin on mean serum vitamin B 12 level, ovalocytosis, MCV, MCH and total WBC count between the metformin-treated and metformin-naive participants. We advocate for vitamin B 12 supplements in this group of patients via the parenteral route of administration, most preferably the intramuscular site injection; in order to prevent the occurrence of vitamin B 12 deficiency among them. Lastly, we recommend the use of serum vitamin B 12 assay and complete blood count (CBC) with peripheral blood films (PBFs) as a reliable way to diagnose and screen for vitamin B 12 deficiency among metformin-treated type 2 DM patients.