Predictor of Vitamin B12 Deficiency in Type 2 Diabetes Mellitus Patients Receiving Metformin: A Cross-Sectional Analysis

Abstract

Background: Metformin remains the first-line pharmacological therapy for type 2 diabetes mellitus (T2DM) because of its proven
efficacy, safety profile, and cardiovascular benefits. However, prolonged metformin therapy has increasingly been associated with
reduced vitamin B12 absorption, potentially leading to biochemical deficiency and clinical manifestations such as anemia, peripheral
neuropathy, cognitive impairment, and worsening diabetic neuropathy. Despite growing awareness, routine screening for vitamin
B12 deficiency among metformin-treated patients is not universally practiced, particularly in resource-limited settings. Identifying
clinical predictors of vitamin B12 deficiency may facilitate early diagnosis and timely intervention.
Methodology: A hospital-based cross-sectional study was conducted in the Department of Medicine, Pt. JNM Medical College and
Dr. B.R.A.M. Hospital, Raipur, Chhattisgarh, over one year. Eighty-five adults with type 2 diabetes mellitus receiving metformin
therapy were included. Demographic characteristics, anthropometric measurements, duration of diabetes, metformin dose, treatment
duration, glycemic indices, hematological parameters, and serum vitamin B12 concentrations were evaluated. Vitamin B12 deficiency
was defined according to standard laboratory reference values. Appropriate statistical analyses including Chi-square test, independent
t-test, Pearson correlation, and multivariable logistic regression were performed, with statistical significance considered at p <0.05.
Results: Among 85 participants, vitamin B12 deficiency was identified in 28 (32.9%). Vitamin B12 deficiency was significantly
associated with longer duration of metformin therapy (>5 years), higher daily metformin dose (≥2000 mg/day), poor glycaemic control
(HbA1c ≥7.0%), and the presence of peripheral neuropathy (all p<0.05) on univariate analysis. Multivariable logistic regression
demonstrated that prolonged metformin therapy (OR 3.42, 95% CI 1.29–9.10; p=0.013), higher daily metformin dose (OR 2.84, 95%
CI 1.08–7.43; p=0.034), and peripheral neuropathy (OR 4.18, 95% CI 1.55–11.24; p=0.005) were independent predictors of vitamin
B12 deficiency, whereas HbA1c was not independently associated after adjustment (p=0.102).
Conclusion: Vitamin B12 deficiency appears to be relatively common among patients with type 2 diabetes mellitus receiving longterm
metformin therapy. Extended treatment duration, higher metformin dosage, and suboptimal glycemic control may independently
predict deficiency. Periodic monitoring of vitamin B12 status may facilitate early detection and reduce long-term neurological and
hematological complications.
Recommendation: Routine vitamin B12 screening should be considered for patients receiving prolonged metformin therapy, particularly
those with poor glycemic control, higher daily doses, or clinical evidence of neuropathy. Larger multicentre prospective studies are
recommended to validate these observations.