{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T12:26:04Z","timestamp":1792412764997,"version":"4.4.0"},"reference-count":41,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T00:00:00Z","timestamp":1412812800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0109878","type":"journal-article","created":{"date-parts":[[2014,10,9]],"date-time":"2014-10-09T18:17:54Z","timestamp":1412878674000},"page":"e109878","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":24,"title":["Higher Prevalence of Metformin-Induced Vitamin B12 Deficiency in Sulfonylurea Combination Compared with Insulin Combination in Patients with Type 2 Diabetes: A Cross-Sectional Study"],"prefix":"10.1371","volume":"9","author":[{"given":"Donghoon","family":"Kang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Seung","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Hye","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Seok","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Bae","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Moon","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Hyun","family":"Ko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,10,9]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.diabet.2010.11.002","article-title":"Metformin and digestive disorders","volume":"37","author":"M Bouchoucha","year":"2011","journal-title":"Diabetes Metab"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.2337\/dc14-S014","article-title":"Standards of medical care in diabetes\u20132014","volume":"37","year":"2014","journal-title":"Diabetes Care"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"193","DOI":"10.2337\/dc08-9025","article-title":"Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes","volume":"32","author":"DM Nathan","year":"2009","journal-title":"Diabetes Care"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4093\/dmj.2011.35.5.431","article-title":"2011 clinical practice guidelines for type 2 diabetes in Korea. Committee of ClinicalPractice Guidelines, Korean Diabetes Association","volume":"35","author":"SH Ko","year":"2011","journal-title":"Diabetes Metab J"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"985","DOI":"10.2337\/dc13-2097","article-title":"Ambulatory treatment of type 2 diabetes in the U.S., 1997\u20132012","volume":"37","author":"LW Turner","year":"2014","journal-title":"Diabetes Care"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"2251","DOI":"10.1001\/archinte.162.19.2251-a","article-title":"Metformin-associated vitamin B12 deficiency","volume":"162","author":"E Andres","year":"2002","journal-title":"Arch Intern Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1097\/SMJ.0b013e3181ce0e4d","article-title":"Metformin-induced vitamin B12 deficiency presenting as a peripheral neuropathy","volume":"103","author":"DS Bell","year":"2010","journal-title":"South Med J"},{"key":"ref8","first-page":"383","article-title":"Should we screen diabetic patients using biguanides for megaloblastic anaemia?","volume":"32","author":"K Filioussi","year":"2003","journal-title":"Aust Fam Physician"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1093\/ageing\/afj042","article-title":"Metformin-related vitamin B12 deficiency","volume":"35","author":"KW Liu","year":"2006","journal-title":"Age Ageing"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"c2181","DOI":"10.1136\/bmj.c2181","article-title":"Long term treatment with metformin in patients with type 2 diabetes and risk of vitamin B-12 deficiency: randomised placebo controlled trial","volume":"340","author":"J de Jager","year":"2010","journal-title":"BMJ"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.2337\/dc09-0606","article-title":"Association of metformin, elevated homocysteine, and methylmalonic acid levels and clinically worsened diabetic peripheral neuropathy","volume":"33","author":"DJ Wile","year":"2010","journal-title":"Diabetes Care"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.jdiacomp.2005.10.005","article-title":"Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus","volume":"21","author":"M Sahin","year":"2007","journal-title":"J Diabetes Complications"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"965","DOI":"10.3346\/jkms.2014.29.7.965","article-title":"Association of Vitamin B12 Deficiency and Metformin Use in Patients with Type 2 Diabetes","volume":"29","author":"SH Ko","year":"2014","journal-title":"J Korean Med Sci"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1365-2362.2004.01381.x","article-title":"GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients","volume":"34","author":"G Schernthaner","year":"2004","journal-title":"Eur J Clin Invest"},{"key":"ref15","unstructured":"Kimberley Standard Drug List. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.ksdl.kamsc.org.au\/dtp\/switching_\" xlink:type=\"simple\">http:\/\/www.ksdl.kamsc.org.au\/dtp\/switching_<\/ext-link> sulphonylureas.html. Accessed 2014 Aug 10."},{"key":"ref16","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1093\/alcalc\/37.5.409","article-title":"Cardioprotective effects of light-moderate consumption of alcohol: a review of putative mechanisms","volume":"37","author":"DP Agarwal","year":"2002","journal-title":"Alcohol Alcoholism"},{"key":"ref17","first-page":"51","article-title":"Higher prevalence and awareness, but lower control rate of hypertension in patients with diabetes than general population: the fifth Korean National Health and Nutrition Examination Survey in 2011. Taskforce Team of Diabetes Fact Sheet of the Korean Diabetes Association","volume":"38","author":"SH Ko","year":"2014"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.diabres.2012.06.001","article-title":"Recommendations for diagnosis and management of metformin-induced vitamin B<sub>12<\/sub> (Cbl) deficiency","volume":"97","author":"EE Mazokopakis","year":"2012","journal-title":"Diabetes Res Clin Pract"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e84","DOI":"10.2337\/dc12-0980","article-title":"Vitamin B(12) deficiency associated with concomitant metformin and proton pump inhibitor use","volume":"35","author":"AN Long","year":"2012","journal-title":"Diabetes Care"},{"key":"ref20","unstructured":"WHO\/UNICEF\/UNU (2001) Iron Deficiency Anemia: Assessment, Prevention, and Control. World Health Organization: 1\u2013130."},{"key":"ref21","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.2337\/diacare.27.2007.S79","article-title":"Nephropathy in diabetes","volume":"27","author":"ME Molitch","year":"2004","journal-title":"Diabetes Care"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0168-8227(99)00112-6","article-title":"Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life","volume":"47","author":"BS Galer","year":"2000","journal-title":"Diabetes research and clinical practice"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1046\/j.1464-5491.2002.00819.x","article-title":"Symptom scoring systems to diagnose distal polyneuropathy in diabetes: the Diabetic Neuropathy Symptom score","volume":"19","author":"JW Meijer","year":"2002","journal-title":"Diabet Med"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/BF00275941","article-title":"Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy","volume":"24","author":"JF Adams","year":"1983","journal-title":"Diabetologia"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3122\/jabfm.2009.05.090044","article-title":"The prevalence of vitamin B(12) deficiency in patients with type 2 diabetes: a cross-sectional study","volume":"22","author":"MC Pflipsen","year":"2009","journal-title":"J Am Board Fam Med"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.2337\/dc11-1582","article-title":"Association of biochemical B<sub>12<\/sub> deficiency with metformin therapy and vitamin B<sub>12<\/sub> supplements: the National Health and Nutrition Examination Survey, 1999\u20132006","volume":"35","author":"L Reinstatler","year":"2012","journal-title":"Diabetes Care"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1177\/14746514040040060701","article-title":"Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study","volume":"4","author":"L Sparre Hermann","year":"2004","journal-title":"The British Journal of Diabetes & Vascular Disease"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/bmj.2.5763.685","article-title":"Vitamin-B12 status of patients on long-term metformin therapy","volume":"2","author":"GH Tomkin","year":"1971","journal-title":"Br Med J"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1056\/NEJM199508313330902","article-title":"Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. The Multicenter Metformin Study Group","volume":"333","author":"RA DeFronzo","year":"1995","journal-title":"N Engl J Med"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1111\/j.1532-5415.2012.03998.x","article-title":"Relationship between vitamin B12 and sensory and motor peripheral nerve function in older adults","volume":"60","author":"K Leishear","year":"2012","journal-title":"J Am Geriatr Soc"},{"key":"ref31","unstructured":"Naha K, Dasari S, Vivek G, Prabhu M (2012) Vitamin B(12) deficiency: an unusual cause for recurrent generalised seizures with pancytopaenia. BMJ Case Rep 2012."},{"key":"ref32","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1093\/ageing\/afl033","article-title":"Clinical relevance of low serum vitamin B<sub>12<\/sub> concentrations in older people: the Banbury B<sub>12<\/sub> study","volume":"35","author":"H Hin","year":"2006","journal-title":"Age Ageing"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/2251-6581-12-17","article-title":"Vitamin B<sub>12<\/sub> deficiency among patients with diabetes mellitus: is routine screening and supplementation justified?","volume":"12","author":"D Kibirige","year":"2013","journal-title":"J Diabetes Metab Disord"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1001\/archinte.1988.00380080016007","article-title":"Pernicious anemia. The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking","volume":"148","author":"R Carmel","year":"1988","journal-title":"Arch Intern Med"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1056\/NEJM198806303182604","article-title":"Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis","volume":"318","author":"J Lindenbaum","year":"1988","journal-title":"N Engl J Med"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1182\/blood.V76.5.871.871","article-title":"Clinical spectrum and diagnosis of cobalamin deficiency","volume":"76","author":"SP Stabler","year":"1990","journal-title":"Blood"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.blre.2006.02.002","article-title":"Diagnosis of megaloblastic anaemias","volume":"20","author":"SN Wickramasinghe","year":"2006","journal-title":"Blood Rev"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1751-553X.2007.00911.x","article-title":"Diagnostic clues to megaloblastic anaemia without macrocytosis","volume":"29","author":"CW Chan","year":"2007","journal-title":"Int J Lab Hematol"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1046\/j.1365-2796.2003.01213.x","article-title":"Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B<sub>12<\/sub> in type 2 diabetes mellitus: a randomized, placebo-controlled trial","volume":"254","author":"MG Wulffele","year":"2003","journal-title":"J Intern Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1001\/archinte.166.18.1975","article-title":"Risk factors of vitamin B<sub>12<\/sub> deficiency in patients receiving metformin","volume":"166","author":"RZ Ting","year":"2006","journal-title":"Arch Intern Med"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.2337\/diacare.23.9.1227","article-title":"Increased intake of calcium reverses vitamin B<sub>12<\/sub> malabsorption induced by metformin","volume":"23","author":"WA Bauman","year":"2000","journal-title":"Diabetes Care"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0109878","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T17:16:57Z","timestamp":1598375817000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0109878"}},"subtitle":[],"editor":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,10,9]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2014,10,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0109878","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10,9]]}}}