Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study
Abstract
CONTEXT: Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use.
OBJECTIVE: To assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS).
DESIGN: Secondary analysis from the DPP/DPPOS. Participants were assigned to the placebo group (PLA) (n = 1082) or the metformin group (MET) (n = 1073) for 3.2 years; subjects in the metformin group received open-label metformin for an additional 9 years.
SETTING: Twenty-seven study centers in the United States.
PATIENTS: DPP eligibility criteria were: elevated fasting glucose, impaired glucose tolerance, and overweight/obesity. The analytic population comprised participants with available stored samples. B12 levels were assessed at 5 years (n = 857, n = 858) and 13 years (n = 756, n = 764) in PLA and MET, respectively.
INTERVENTION: Metformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS).
MAIN OUTCOME MEASURES: B12 deficiency, anemia, and peripheral neuropathy.
RESULTS: Low B12 (≤ 203 pg/mL) occurred more often in MET than PLA at 5 years (4.3 vs 2.3%; P = .02) but not at 13 years (7.4 vs 5.4%; P = .12). Combined low and borderline-low B12 (≤ 298 pg/mL) was more common in MET at 5 years (19.1 vs 9.5%; P < .01) and 13 years (20.3 vs 15.6%; P = .02). Years of metformin use were associated with increased risk of B12 deficiency (odds ratio, B12 deficiency/year metformin use,…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 1,082 participants or records.
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