Prevalence and Clinical Predictors of Vitamin B12 Deficiency in Patients Receiving Long-Term Metformin Therapy

Abstract

Background: Metformin is a very common first-line drug for type 2 diabetes mellitus (T2DM). It works, is inexpensive and generally well tolerated, but has been linked to decreased absorption of vitamin B12 and subsequent deficiency when used for a long time. Vitamin B12 deficiency can cause symptoms such as anaemia, macrocytosis, and peripheral neuropathy and cognitive dysfunction that are potentially indistinguishable from diabetic neuropathy. The aim of this study was to establish a prevalence rate of vitamin B12 deficiency and its clinical predictors among patients on long-term metformin therapy.

Methods: This descriptive cross sectional study was carried out on the period of January 2022 to June 2023 at Department of Medicine, Dhaka Central International Medical College Hospital, Adabor, Dhaka, Bangladesh. In the present study, 85 adult patients of type 2 Diabetes mellitus (T2DM) having continued use of metformin therapy for at least 1 year from their last visit were recruited using non-probability consecutive sampling technique. Demographic parameters, diabetes duration, dose and duration of metformine, dietary pattern, use of proton pump inhibitors, haematological parameters and neurological symptoms were recorded. Vitamin B12 level <200 pg/mL was considered deficient, 200 to 300 pg/mL was considered borderline and >300 pg/mL was considered normal. Binary logistic regression was used to determine the independent predictors of B12 deficiency.

Results: The mean age of the participants was 55.6 ± 10.8 years, and 55.3% were male. Vitamin B12 deficiency was identified in 24 patients, giving an overall prevalence of 28.2%, while 25.9% had borderline vitamin B12 levels. Deficiency increased with longer metformin exposure, from 11.8% among patients treated for 1–3 years to 38.1% among those treated for more than six years. It was also more frequent among patients receiving more than 1,500 mg/day. Longer metformin duration, higher daily dose and concurrent proton-pump inhibitor use were independent predictors. Deficient patients had lower haemoglobin levels and higher frequencies of macrocytosis, anaemia and peripheral neuropathy.

Conclusion: Vitamin B12 deficiency was common among patients receiving long-term metformin therapy. The risk was particularly high among patients exposed to higher doses, longer treatment durations and concurrent acid-suppressive therapy. Periodic assessment of vitamin B12 status should be considered in high-risk patients, especially those presenting with anaemia or neuropathic symptoms.