Association of metformin use with vitamin B₁₂ deficiency in the institutionalized elderly

Elderly people living in long term care institutions are particularly at risk of vitamin B₁₂ deficiency. The prevalence of vitamin B₁₂ deficiency was 34.9% among the 1996 institutionalized elderly residents in our previous study. The present retrospective study evaluated the association of metformin use with vitamin B₁₂ deficiency in the same group of patients. Of 1996 patients, 507 (25.4%) had diabetes, of which 188 received metformin treatment. The prevalence of vitamin B₁₂ deficiency in diabetic patients taking metformin was 53.2% compared with 31% (P < 0.001) of diabetic patients not taking metformin and 33.3% (P < 0.001) of those without diabetes. Among the vitamin B₁₂ deficient patients, diabetic patients taking metformin had lower serum vitamin B₁₂ concentration (97 pmol/L) than the diabetic patients not taking metformin (113 pmol/L, P < 0.001) and those without diabetes (111 pmol/L, P < 0.001). Subanalysis of 174 metformin users found that dose and duration of metformin use were significantly associated with vitamin B₁₂ deficiency. Adjusted odds ratio for those taking metformin ≥1500 mg /day was 2.72 (95% CI 1.11-6.7, P = 0.029) compared with those using metformin <1000mg/day. Adjusted odds ratio for those taking metformin>4 years was 3.00 (95% CI 1.35-6.68, P = 0.007) compared with those taking metformin <2 years. Prevalence of vitamin B₁₂ deficiency among those taking metformin ≥1500 mg/day for >2 years was 75.9% and was more than 2 times that of patients taking metformin <1500 mg/day for ≤2 years (35.3%). In conclusion, metformin use is associated with increased risk and severity of vitamin B₁₂ deficiency in the institutionalized elderly residents. Patients taking metformin ≥1500 mg/day for >2 years are particularly at risk. Testing for vitamin B₁₂ status before and regularly after the start of metformin may be considered.