Metformin-Induced Vitamin B12 Deficiency among Type 2 Diabetes Mellitus' Patients: A Systematic Review

Background: Type 2 diabetes mellitus is one of the most globally common chronic diseases. Metformin is the most popular prescribed medication for the treatment of diabetes. Studies suggest that metformin is associated with vitamin B12 deficiency, which may impart adverse health complications. Objective: This review screens the literature to clarify the effect of metformin on vitamin B12 deficiency among type 2 diabetes mellitus patients. Methods: Google Scholar, PubMed, Research Gate, and Semantic Scholar, were searched for the association between metformin intake and vitamin B12 deficiency in type 2 diabetes mellitus patients using relevant keywords and their combinations. Selected studies were those conducted on patients taking metformin with no vitamin B12 supplement. Nineteen studies (fifteen observational studies and four randomized controlled trials) met the inclusion criteria. These studies were assessed for design, setting, study population, and overall quality. Results: There is a positive correlation between metformin intake and vitamin B12 deficiency. This has been accompanied by increased homocysteine and decreased folate levels. Despite the refuting of the findings, most studies showed that higher doses of metformin were strongly associated with lower vitamin B12 levels, while the duration of treatment was not. Conclusion: Regular measurement of vitamin B12 levels during long-term metformin treatment is recommended. A clear policy should be in place to illuminate the importance of this screening in preventing vitamin B12 deficiency complications. Taking therapeutic supplements or injections of vitamin B12 along with a vitamin B12-rich diet may decrease the incidence of its deficiency in diabetic patients taking metformin.