{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T18:01:17Z","timestamp":1788026477960,"version":"build-2784847793"},"reference-count":29,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T00:00:00Z","timestamp":1579824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims\/Introduction<\/jats:title><jats:p>Metformin therapy has been associated with vitamin\u00a0B<jats:sub>12<\/jats:sub> (VB12) deficiency, but information regarding this adverse effect in Asian populations is limited. We have now examined the relationship between metformin use and VB12 status in individuals with type\u00a02 diabetes mellitus in Japan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and Methods<\/jats:title><jats:p>This cross\u2010sectional study was carried out with type\u00a02 diabetes mellitus patients treated (Met group,\u00a0<jats:italic>n<\/jats:italic>\u00a0=\u00a0122) or not treated (control group, <jats:italic>n<\/jats:italic>\u00a0=\u00a063) with metformin. The primary end\u2010point was the difference in the serum concentration of homocysteine, a marker of VB12 activity, between the two groups. The serum concentrations of VB12, blood hemoglobin level and mean corpuscular volume were also compared between the groups. Subset analysis was carried out with individuals aged \u226570\u00a0years. The potential correlation between the daily dose or duration of metformin treatment and the other measured parameters was also examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The level of homocysteine, as well as the VB12 level, hemoglobin concentration and mean corpuscular volume, did not differ significantly between the control and treated with metformin groups. The level of homocysteine was positively and that of VB12 negatively correlated with the daily dose of metformin. Among elderly individuals, the hemoglobin level was significantly lower in the treated with metformin group than in the control group, although the mean corpuscular volume was similar in the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The risk of VB12 deficiency during metformin treatment appears to be low in Japanese type\u00a02 diabetes mellitus patients. However, high doses of metformin might result in a moderate decrease in the circulating VB12 level, as well as in anemia in elderly individuals.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.13200","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T16:44:58Z","timestamp":1577119498000},"page":"917-922","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Relationship between metformin use and vitamin\u00a0B<sub>12 <\/sub>status in patients with type\u00a02 diabetes in Japan"],"prefix":"10.1111","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-7183","authenticated-orcid":false,"given":"Kenji","family":"Sugawara","sequence":"first","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6964-5147","authenticated-orcid":false,"given":"Yuko","family":"Okada","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3035-4155","authenticated-orcid":false,"given":"Yushi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1577-2401","authenticated-orcid":false,"given":"Kazuhiko","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Division of General Internal Medicine Department of Internal Medicine Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0432-4366","authenticated-orcid":false,"given":"Wataru","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Division of Diabetes and Endocrinology Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"issue":"1","key":"e_1_2_7_2_1","first-page":"45","article-title":"Metformin\u2010associated lactic acidosis requiring hospitalization. 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