Retrospective study found B12 deficiency correlated with dose and duration of metformin therapy. B12 deficit defined as less than 150. N was 155 patients. Mechanism is inhibition of calcium dependent ileal absorption of B12-intrinsic factor, which calcium supplementation can reverse.
Along with acid inhibitors (PPI's H2 blockers, metformin is most common cause of B12 deficiency. Odds ratio is 2.88 for each i gram increment and 2.39 for use > 3 years.
In one study 6 percent of cases of B12 deficiency had associated metformin use (Br M J 1971) ,