Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/133646
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Type: | Journal article |
Title: | Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial |
Author: | Cluver, C.A. Hiscock, R. Decloedt, E.H. Hall, D.R. Schell, S. Mol, B.W. Brownfoot, F. Kaitu'u-Lino, T.J. Walker, S.P. Tong, S. |
Citation: | BMJ: British Medical Journal, 2021; 374:n2103-1-n2103-10 |
Publisher: | BMJ |
Issue Date: | 2021 |
ISSN: | 0959-8146 1756-1833 |
Statement of Responsibility: | Catherine A Cluver, Richard Hiscock, Eric H Decloedt, David R Hall, Sonja Schell, Ben W Mol, Fiona Brownfoot, Tu, uhevaha J Kaitu, u-Lino, Susan P Walker, Stephen Tong |
Abstract: | OBJECTIVE To evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia. DESIGN Randomised, double blind, placebo controlled trial. SETTING Referral hospital in Cape Town, South Africa. PARTICIPANTS 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks’ gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo. INTERVENTION 3 g of oral extended release metformin or placebo daily, in divided doses, until delivery. MAIN OUTCOME MEASURE The primary outcome was prolongation of gestation. RESULTS 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. CONCLUSIONS This trial suggests that extended release metformin can prolong gestation in women with preterm preeclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible. TRIAL REGISTRATION Pan African Clinical Trial Registry PACTR201608001752102 https://pactr.samrc.ac.za/. |
Keywords: | Humans Pre-Eclampsia Premature Birth Metformin Vascular Endothelial Growth Factor Receptor-1 Delayed-Action Preparations Treatment Outcome Double-Blind Method Gestational Age Pregnancy Time Factors Adult Infant, Newborn Female Watchful Waiting Endoglin Placenta Growth Factor Proof of Concept Study |
Rights: | © 2021, BMJ Publishing Group Ltd This article is Open Access, published under the terms of a Creative Commons licence. Please refer back to the article to check the applicable licence (details are in the article Footnotes). Articles published under CC-BY-NC permit non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited. Permission only needs to be obtained for commercial use and can be done via the RightsLink system below. Articles published under the CC-BY permit unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
DOI: | 10.1136/bmj.n2103 |
Published version: | http://dx.doi.org/10.1136/bmj.n2103 |
Appears in Collections: | Obstetrics and Gynaecology publications |
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