Association of Biochemical B12 Deficiency With Metformin Therapy and Vitamin B12 Supplements

Diabetes Care
Q1
Jan 2012
Citations:292
Influential Citations:10
Observational Studies (Human)
81
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Methods
NHANES 1999-2006; nationally representative cross-sectional sample of U.S. adults aged ≥50 years. Participants categorized as: type 2 diabetes on metformin (n=575), type 2 diabetes not on metformin (n=1,046), and without diabetes (n=6,867). Biochemical B12 deficiency defined as serum B12 ≤148 pmol/L; borderline deficiency 148-221 pmol/L. Serum B12 measured by Quantaphase II assay. Analyses used survey weights; logistic regression and polytomous logistic regression; adjustments included age, BMI, insulin use, and B12 supplement use.
Intervention
Vitamin B12-containing supplements; daily intake categories: 0 mg (no supplement), 0-6 mg/day, 6-25 mg/day, >25 mg/day; duration not reported; taken as dietary supplement.
Results
Metformin therapy is associated with higher prevalence of biochemical B12 deficiency among adults with type 2 diabetes (adjusted OR 2.92; 95% CI 1.28-6.66) and borderline deficiency (OR 2.16; 95% CI 1.22-3.85). Vitamin B12 supplementation reduces risk of borderline deficiency in type 2 diabetes (OR 0.43; 95% CI 0.23-0.81) and reduces biochemical deficiency in those without diabetes (OR 0.26; 95% CI 0.17-0.38) and borderline deficiency (OR 0.27; 95% CI 0.21-0.35). Among diabetics on metformin using supplements, higher daily B12 doses (>6 mg) were associated with a marked reduction in biochemical deficiency (1.8%) versus 0-6 mg/day (14.1%), with a dose-response (P=0.0273). In diabetics not on metformin and in those without diabetes, supplement use also reduced deficiency risk. No clear monotonic increase in biochemical deficiency with longer duration of metformin use (4.1% <1 year; 6.3% 1-3 years; 8.1% ≥10 years; P=0.32). Conclusions: Metformin is linked to higher biochemical B12 deficiency; the IOM-recommended 2.4 (mg) daily B12 and typical 6 mg multivitamins may be insufficient for metformin users; higher B12 supplementation may help prevent deficiency, especially at higher doses; further research is warranted.
Limitations
Cross-sectional NHANES design; cannot infer causality; metformin and supplement use relied on self-report; B12 status based on serum B12 with limited MMA data; missing data on some covariates; analysis restricted to adults ≥50 years; possible misclassification of diabetes type; generalizability limited to older adults.

Abstract

OBJECTIVE To describe the prevalence of biochemical B12 deficiency in adults with type 2 diabetes taking metformin compared with those not taking metformin and those without diabetes, and explore whether this relationship is modified by vitamin B12 s...