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.