南非斯坦陵布什大学Catherine A Cluver团队研究了二甲双胍缓释剂延长早产先兆子痫患者的妊娠的效果。相关论文于2021年9月23日发表在《英国医学杂志》上。

为了评估二甲双胍缓释剂是否可用于延长因早产先兆子痫接受期待治疗的妇女的妊娠期，研究组在南非开普敦的转诊医院进行了一项随机、双盲、安慰剂对照试验。共有180名妊娠26+0周至31+6周的早产先兆子痫妇女接受期待治疗，将其随机分组，其中90名接受二甲双胍缓释剂治疗，90名接受安慰剂治疗。主要结局为妊娠期延长。

180名参与者中，有一名女性在服用任何试验药物前分娩。二甲双胍组从随机分组到分娩的中位时间为17.7天，安慰剂组为10.1天，中位差异为7.6天。在继续服用任何剂量试验药物的患者中，二甲双胍组的妊娠期中位延长时间为17.5天，而安慰剂组为7.9天，中位差异为9.6天。

在服用全剂量二甲双胍的患者中，二甲双胍组的妊娠期中位延长时间为16.3天，而安慰剂组为4.8天，中位差异为11.5天。母体、胎儿和新生儿的综合结局和循环中可溶性fms样酪氨酸激酶-1、胎盘生长因子和可溶性内质酸的浓度没有差异。在二甲双胍组，新生儿体重无显著增加，在新生儿病房的停留时间缩短。未观察到与试验药物相关的严重不良事件，尽管腹泻在二甲双胍组更为常见。

研究结果表明，二甲双胍缓释剂可延长早产先兆子痫妇女的妊娠期，但仍需进一步试验。它提供了治疗早产先兆子痫的潜力。

附：英文原文

Title: Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial

Author: 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

Issue&Volume: 2021/09/23

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 pre-eclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible.

DOI: 10.1136/bmj.n2103

Source: https://www.bmj.com/content/374/bmj.n2103