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Current treatment is focused on reducing hyperglycaemia, by dietary and lifestyle intervention and, if glycaemic targets are not reached, insulin. Metformin is an oral blood glucose lowering drug and considered safe during pregnancy. It improves insulin sensitivity and has shown advantages, specifically regarding pregnancy-related outcomes and patient satisfaction, compared with insulin therapy. However, the role of metformin in addition to usual care is inconclusive and long-term outcome of metformin exposure in utero are lacking. The primary aim of this study is to investigate the early addition of metformin on pregnancy and long-term outcomes in GDM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>The Pregnancy Outcomes: Effects of Metformin study is a multicentre, open-label, randomised, controlled trial. Participants include women with GDM, between 16 and 32 weeks of gestation, who are randomised to either usual care or metformin added to usual care, with insulin rescue in both groups. Metformin is given up to 1\u2009year after delivery. The study consists of three phases (A\u2013C): A\u2014until 6 weeks after delivery; B\u2014until 1\u2009year after delivery; C\u2014observational study until 20 years after delivery. During phase A, the primary outcome is a composite score consisting of: (1) pregnancy-related hypertension, (2) large for gestational age neonate, (3) preterm delivery, (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia, (8) neonatal intensive care admission. During phase B and C the primary outcome is the incidence of T2DM and (weight) development in mother and child.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>The study was approved by the Central Committee on Research Involving Human Subjects in the Netherlands. Results will be submitted for publication in peer-reviewed journals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial registration number<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT02947503\">NCT02947503<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2021-056282","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T17:03:22Z","timestamp":1648659802000},"page":"e056282","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Pregnancy Outcomes: Effects of Metformin (POEM) study: a protocol for a long-term, multicentre, open-label, randomised controlled trial in gestational diabetes mellitus"],"prefix":"10.1136","volume":"12","clinical-trial-number":[{"clinical-trial-number":"nct02947503","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-8231","authenticated-orcid":false,"given":"Eline G M","family":"van Hoorn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-6551","authenticated-orcid":false,"given":"Peter R","family":"van Dijk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3984-2163","authenticated-orcid":false,"given":"Jelmer R","family":"Prins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen L","family":"Lutgers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaas","family":"Hoogenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1362-4501","authenticated-orcid":false,"given":"Jan Jaap H M","family":"Erwich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-0019","authenticated-orcid":false,"given":"Adriaan","family":"Kooy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2022,3,30]]},"reference":[{"key":"2023030803131641000_12.3.e056282.1","doi-asserted-by":"crossref","DOI":"10.1007\/s11892-015-0699-x","article-title":"Prevalence of gestational diabetes and risk of progression to type 2 diabetes: a global perspective","volume":"16","author":"Zhu","year":"2016","journal-title":"Curr Diab Rep"},{"key":"2023030803131641000_12.3.e056282.2","doi-asserted-by":"publisher","DOI":"10.3109\/14767058.2011.587921"},{"key":"2023030803131641000_12.3.e056282.3","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.diabres.2017.03.030","article-title":"Prevalence of gestational diabetes mellitus in Europe: a meta-analysis","volume":"129","author":"Eades","year":"2017","journal-title":"Diabetes Res Clin Pract"},{"key":"2023030803131641000_12.3.e056282.4","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-019-0406-1"},{"key":"2023030803131641000_12.3.e056282.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2013.11.003"},{"key":"2023030803131641000_12.3.e056282.6","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.2337\/dc07-s203","article-title":"The human placenta in gestational diabetes mellitus. the insulin and cytokine network","volume":"30 Suppl 2","author":"Desoye","year":"2007","journal-title":"Diabetes Care"},{"key":"2023030803131641000_12.3.e056282.7","doi-asserted-by":"crossref","first-page":"S112","DOI":"10.2337\/dc07-s202","article-title":"Cellular mechanisms for insulin resistance in normal pregnancy and gestational diabetes","volume":"30 Suppl 2","author":"Barbour","year":"2007","journal-title":"Diabetes Care"},{"key":"2023030803131641000_12.3.e056282.8","doi-asserted-by":"crossref","unstructured":"Hanley AJ . 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