A study published in the Archives of Internal Medicine (2006; 166(18):1975–1979) found an association between metformin use and vitamin B12 deficiency. In this case–control study, people with diabetes taking metformin had significantly lower vitamin B12 levels than matched controls. Lower B12 levels were linked with higher doses and longer duration of metformin use. After three years of use, the risk of B12 deficiency was more than twice as high.