{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:56:08Z","timestamp":1793127368817,"version":"4.5.0"},"reference-count":26,"publisher":"BMJ","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Objective<\/jats:title>\n            <jats:p>To evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Design<\/jats:title>\n            <jats:p>Randomised, double blind, placebo controlled trial.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Setting<\/jats:title>\n            <jats:p>Referral hospital in Cape Town, South Africa.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Participants<\/jats:title>\n            <jats:p>180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks\u2019 gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Intervention<\/jats:title>\n            <jats:p>3 g of oral extended release metformin or placebo daily, in divided doses, until delivery.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Main outcome measure<\/jats:title>\n            <jats:p>The primary outcome was prolongation of gestation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Of 180 participants, one woman delivered before taking any trial drug. The median time from randomisation to delivery was 17.7 days (interquartile range 5.4-29.4 days; n=89) in the metformin arm and 10.1 (3.7-24.1; n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39, 95% confidence interval 0.99 to 1.95; P=0.057). Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (interquartile range 5.4-28.7; n=76) days compared with 7.9 (3.0-22.2; n=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 95% confidence interval 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (interquartile range 4.8-28.8; n=40) days compared with 4.8 (2.5-15.4; n=61) days in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% confidence interval 1.14 to 2.88). Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ. In the metformin arm, birth weight increased non-significantly and length of stay decreased in the neonatal nursery. No serious adverse events related to trial drugs were observed, although diarrhoea was more common in the metformin arm.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This trial suggests that extended release metformin can prolong gestation in women with preterm pre-eclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Trial registration<\/jats:title>\n            <jats:p>\n              Pan African Clinical Trial Registry PACTR201608001752102\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/pactr.samrc.ac.za\/\">https:\/\/pactr.samrc.ac.za\/<\/jats:ext-link>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1136\/bmj.n2103","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T01:31:20Z","timestamp":1632360680000},"page":"n2103","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":98,"title":["Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0406-8964","authenticated-orcid":false,"given":"Catherine A","family":"Cluver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hiscock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H","family":"Decloedt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Schell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Brownfoot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tu\u2019uhevaha J","family":"Kaitu\u2019u-Lino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan P","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"2021092222250981000_374.sep22_11.n2103.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2013.05.005"},{"key":"2021092222250981000_374.sep22_11.n2103.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32335-7"},{"key":"2021092222250981000_374.sep22_11.n2103.3","first-page":"28","article-title":"Maternal deaths due to hypertensive disorders of pregnancy: data from the 2014-2016 Saving Mothers\u2019 Report","volume":"28","author":"Moodley","year":"2018","journal-title":"Obstet Gynaecol Forum"},{"key":"2021092222250981000_374.sep22_11.n2103.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.08.019"},{"key":"2021092222250981000_374.sep22_11.n2103.5","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000000472"},{"key":"2021092222250981000_374.sep22_11.n2103.6","doi-asserted-by":"publisher","DOI":"10.1007\/BF03401783"},{"key":"2021092222250981000_374.sep22_11.n2103.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.08.004"},{"key":"2021092222250981000_374.sep22_11.n2103.8","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000001727"},{"key":"2021092222250981000_374.sep22_11.n2103.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2018.07.019"},{"key":"2021092222250981000_374.sep22_11.n2103.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2020.09.014"},{"key":"2021092222250981000_374.sep22_11.n2103.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2015.12.019"},{"key":"2021092222250981000_374.sep22_11.n2103.12","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12501"},{"key":"2021092222250981000_374.sep22_11.n2103.13","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/6547019"},{"key":"2021092222250981000_374.sep22_11.n2103.14","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10803"},{"key":"2021092222250981000_374.sep22_11.n2103.15","first-page":"22","article-title":"Understanding expectant management of pre-eclampsia","volume":"26","author":"Hall","year":"2016","journal-title":"Obstet Gynaecol Forum"},{"key":"2021092222250981000_374.sep22_11.n2103.16","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-025809"},{"key":"2021092222250981000_374.sep22_11.n2103.17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"2021092222250981000_374.sep22_11.n2103.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2017.12.011"},{"key":"2021092222250981000_374.sep22_11.n2103.19","doi-asserted-by":"crossref","unstructured":"Kiserud T Piaggio G Carroli G . 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