{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:16:58Z","timestamp":1792167418864,"version":"4.4.0"},"reference-count":40,"publisher":"The Endocrine Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context:<\/jats:title>\n                    <jats:p>Vitamin B12 deficiency may occur with metformin treatment, but few studies have assessed risk with long-term use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>To assess the risk of B12 deficiency with metformin use in the Diabetes Prevention Program (DPP)\/DPP Outcomes Study (DPPOS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting:<\/jats:title>\n                    <jats:p>Twenty-seven study centers in the United States.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interventions:<\/jats:title>\n                    <jats:p>Metformin 850 mg twice daily vs placebo (DPP), and open-label metformin in the metformin group (DPPOS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures:<\/jats:title>\n                    <jats:p>B12 deficiency, anemia, and peripheral neuropathy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Low B12 (\u2264 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 (\u2264 298 pg\/mL) was more common in MET at 5 years (19.1 vs 9.5%; P &amp;lt; .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, 1.13; 95% confidence interval, 1.06\u20131.20). Anemia prevalence was higher in MET, but did not differ by B12 status. Neuropathy prevalence was higher in MET with low B12 levels.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Long-term use of metformin in DPPOS was associated with biochemical B12 deficiency and anemia. Routine testing of vitamin B12 levels in metformin-treated patients should be considered.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2015-3754","type":"journal-article","created":{"date-parts":[[2016,2,22]],"date-time":"2016-02-22T13:01:53Z","timestamp":1456146113000},"page":"1754-1761","source":"Crossref","is-referenced-by-count":452,"title":["Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study"],"prefix":"10.1210","volume":"101","author":[{"given":"Vanita R.","family":"Aroda","sequence":"first","affiliation":[{"name":"MedStar Health Research Institute (V.R.A.), Hyattsville, Maryland 20782"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Edelstein","sequence":"additional","affiliation":[{"name":"George Washington University (S.L.E., M.G.T.), Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B.","family":"Goldberg","sequence":"additional","affiliation":[{"name":"University of Miami (R.B.G.), Miami, Florida 33146"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Knowler","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (W.C.K.), Phoenix, Arizona 85014"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santica M.","family":"Marcovina","sequence":"additional","affiliation":[{"name":"University of Washington (S.M.M.), Seattle, Washington 98185"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor J.","family":"Orchard","sequence":"additional","affiliation":[{"name":"University of Pittsburgh (T.J.O.), Pittsburgh, Pennsylvania 15260"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Bray","sequence":"additional","affiliation":[{"name":"Pennington Biomedical Research Institute (G.A.B.), Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Schade","sequence":"additional","affiliation":[{"name":"University of New Mexico (D.S.S.), Albuquerque, New Mexico 87131"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marinella G.","family":"Temprosa","sequence":"additional","affiliation":[{"name":"George Washington University (S.L.E., M.G.T.), Rockville, MD 20852"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil H.","family":"White","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine (N.H.W.), St. Louis, Missouri 63110"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill P.","family":"Crandall","sequence":"additional","affiliation":[{"name":"Albert Einstein College of Medicine (J.P.C.), Bronx, New York 10461"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Diabetes Prevention Program Research 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