Comparison of Patients Receiving Long-Term Metformin Therapy and Vitamin B₁₂ Monitoring

Background: Metformin may cause vitamin B₁₂ deficiency that can present with symptoms of peripheral neuropathy. Lack of vitamin B₁₂ serum concentration monitoring could result in vitamin B₁₂ deficiency progression, worsening of symptoms, and unnecessary medication. Objectives: The purpose of this study was to (a) compare the influence of the rate of symptoms consistent with vitamin B₁₂ deficiency on obtaining vitamin B₁₂ serum concentrations in patients using metformin; (b) assess if vitamin B₁₂ serum concentrations were ordered as a routine monitoring parameter. Methods: This retrospective case-control study evaluated patients receiving metformin. Patients in the case group had documented symptoms or diagnosis of peripheral neuropathy or macrocytic anemia, while those in the control group did not. The primary outcome was frequency of vitamin B₁₂ serum concentration assessment. The secondary outcomes included frequency of vitamin B₁₂ serum concentration assessment for patients presenting with symptoms or diagnosis of peripheral neuropathy or macrocytic anemia. Results: Analysis included 355 patients (116 cases, 239 controls). The cases were 5 times more likely to have a serum vitamin B₁₂ serum concentrations drawn versus controls (odds ratio [OR] = 5.83, 95% confidence interval [CI] = 3.47-9.77, P < .001). Patients with a diagnosis of peripheral neuropathy or macrocytic anemia were 4 times more likely to have a serum vitamin B₁₂ concentration drawn than those who did not (peripheral neuropathy: OR = 4.92, 95% CI = 2.95-8.21, P < .001; macrocytic anemia: OR = 5.41, 95% CI = 1.30-20.97, P = .007). Conclusions: Cases were more likely to have vitamin B₁₂ serum concentrations assessed than patients without symptoms. The majority of patients taking metformin did not have routine vitamin B₁₂ serum concentration assessments for medication adverse event monitoring.