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Long-term metformin use (the first-line type 2 diabetes drug) can lower B12 in a dose- and duration-dependent way: in the Diabetes Prevention Program Outcomes Study (Aroda and colleagues, The Journal of Clinical Endocrinology & Metabolism , 2016, roughly 1,700 participants), low B12 at 5 years occurred in 4.3 percent of metformin users versus 2.3 percent on placebo, and the gap widened with continued use

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