Association of vitamin B₁₂ deficiency and metformin use in patients with type 2 diabetes

We evaluated the prevalence of vitamin B₁₂ deficiency and associated factors in type 2 diabetes patients using metformin. A total of 799 type 2 diabetes patients using metformin was enrolled. Vitamin B₁₂ and folate levels were quantified by chemiluminescent enzyme immunoassay. Vitamin B₁₂ deficiency was defined as vitamin B₁₂=300 pg/mL without folate deficiency (folate>4 ng/mL). The prevalence of vitamin B₁₂ deficiency in metformin-treated type 2 diabetes patients was 9.5% (n=76), and the mean vitamin B₁₂ level was 662.5±246.7 pg/mL. Vitamin B₁₂ deficient patients had longer duration of metformin use (P<0.001) and higher daily metformin dose (P<0.001) than non-deficient patients. Compared with daily metformin dose of ≤1,000 mg, the adjusted odds ratio for 1,000-2,000 mg, and =2,000 mg were 2.52 (95% CI, 1.27-4.99, P=0.008) and 3.80 (95% CI, 1.82-7.92, P<0.001). Compared with metformin use of <4 yr, the adjusted odds ratios for 4-10 yr, and ≥10 yr were 4.65 (95% CI, 2.36-9.16, P<0.001) and 9.21 (95% CI, 3.38-25.11, P<0.001), respectively. In conclusion, our study indicates that patients with type 2 diabetes treated with metformin should be screened for vitamin B₁₂ deficiency, especially at higher dosages (>1,000 mg) and longer durations (=4 yr) of treatment.