Factors associated with an increased risk of vitamin B12 deficiency in patients with type 2 diabetes mellitus on metformin

Background

Metformin is used to treat type 2 diabetes mellitus, but prolonged use has been associated with vitamin B₁₂ deficiency. Many other factors have also been associated with vitamin B₁₂ deficiency. Studies on the possible additive effect of risk factors for developing a vitamin B₁₂ deficiency are lacking.

Aim

The objective of this study was to assess the correlation between other known risk factors for vitamin B₁₂ deficiency among patients with type 2 diabetes mellitus prescribed metformin who had a vitamin B₁₂ deficiency.

Method

For inclusion in this single-centre, retrospective cohort study, patients needed to be at least 18 years old, diagnosed with type 2 diabetes, taking metformin for at least 2 years and actively taking metformin during the study period. The primary outcome was the rate of low B₁₂ levels with metformin. Secondary outcomes were risk factors associated with B₁₂ deficiency. The patient and clinical characteristics were compared between the two study groups using Student's t-test for continuous variables and chi-squared tests for categorical variables. This project was exempt due to the local policy requirements that constitute research by the University of Arkansas for Medical Sciences Institutional Review Board (IRB) (IRB Program Manager, 11 August 2021). The justification for this ethics exemption was as follows: the project was determined to be of minimal risk to privacy of subjects because the research team had mechanisms to protect the personal health identifiers from improper use or disclosure; to destroy the identifiers at the earliest opportunity consistent with the conduct of research, and provided assurance that the identifiers will not be re-used or disclosed to any other person or entity, except as required by law, for authorised oversight of the research project, or for other research as permitted by the HIPAA regulations.

Results

A total of 387 patients were included in this study, from which 364 patients had a vitamin B₁₂ deficiency. The cohort was an average 69-years-old and predominantly female (66%). No risk factors were associated with a higher incidence of B₁₂ deficiency. Patient age (p = 0.0063) and time on metformin (p = 0.0144) were significantly and negatively correlated with B12 deficiency.

Conclusion

Younger age and shorter duration of metformin use may increase the risk of vitamin B₁₂ deficiency. Although guidelines recommend occasional checks, only 21% of patients had vitamin B₁₂ levels assessed during the study period.