{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:49:05Z","timestamp":1774658945931,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T00:00:00Z","timestamp":1526256000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004719","name":"LifeScan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004719","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009947","name":"Merck Sharp and Dohme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009947","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004191","name":"Novo Nordisk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004191","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To study the effects of metformin, as compared to placebo, on serum levels of vitamin D (25\u2010hydroxyvitamin D [25(OH)D]) in patients with advanced type 2 diabetes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      In the HOME trial, a randomized placebo\u2010controlled trial, 390 insulin\u2010treated patients with type 2 diabetes were treated with 850\u2009mg metformin or placebo thrice daily for 52\u2009months. In a\n                      <jats:italic>post\u2010hoc<\/jats:italic>\n                      analysis, we examined changes in the combined levels of 25(OH)D\n                      <jats:sub>2<\/jats:sub>\n                      and 25(OH)D\n                      <jats:sub>3<\/jats:sub>\n                      at 4 and 16\u2009months during the study.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mean combined 25(OH)D at baseline was 68.2\u2009nmoL\/L (95% confidence interval [CI]: 65.5\u201071.1). In mixed model analysis, metformin, as compared to placebo, had no effect on 25(OH)D levels during 16\u2009months (coefficient: 1.002 per month, multiplicative model; 95% CI: 0.998\u20101.006,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.30). Metformin was associated with a small increase of 25(OH)D\n                      <jats:sub>2<\/jats:sub>\n                      (coefficient: 1.012 per month; 95% CI: 1.003\u20101.021,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u2009.008). However, 25(OH)D\n                      <jats:sub>2<\/jats:sub>\n                      is only a very small fraction (3%) of 25(OH)D. Seasonal variation had the biggest impact on 25(OH)D levels. Vitamin B12 levels were not associated with the levels of 25(OH)D.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metformin had no effect on serum 25(OH)D during 16\u2009months in the setting of a clinical randomized controlled trial in patients with type 2 diabetes. Our results show that metformin doesn't lead to vitamin D deficiency.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.13327","type":"journal-article","created":{"date-parts":[[2018,4,17]],"date-time":"2018-04-17T23:09:42Z","timestamp":1524006582000},"page":"1951-1956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Long\u2010term treatment with metformin in type 2 diabetes and vitamin\n                    <scp>D<\/scp>\n                    levels:\n                    <scp>A<\/scp>\n                    <i>post\u2010hoc<\/i>\n                    analysis of a randomized placebo\u2010controlled trial"],"prefix":"10.1111","volume":"20","author":[{"given":"Mattijs","family":"Out","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Bethesda Hospital Hoogeveen \u2013 Care Group Treant  Hoogeveen The Netherlands"},{"name":"Bethesda Diabetes Research Center Hoogeveen  Hoogeveen The Netherlands"},{"name":"Department of Internal Medicine Medisch Spectrum Twente  Enschede The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebe M. C.","family":"Top","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Bethesda Hospital Hoogeveen \u2013 Care Group Treant  Hoogeveen The Netherlands"},{"name":"Bethesda Diabetes Research Center Hoogeveen  Hoogeveen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Lehert","sequence":"additional","affiliation":[{"name":"Department of Statistics, Faculty of Economics Facult\u00e9s Universitaires Catholiques de Mons, Louvain Academy  Mons Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Casper A.","family":"Schalkwijk","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiovascular Research Institute Maastricht Maastricht University Medical Center  Maastricht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-3223","authenticated-orcid":false,"given":"Coen D. 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