JAMA：早期应用二甲双胍治疗妊娠期糖尿病：一项随机临床试验

2023-10-07 来源：JAMA

本文由小咖机器人翻译整理

期刊来源：JAMA

文献发表时间：2023-10-03

原文链接：https://jamanetwork.com/journals/jama/article-abstract/2810387

关键点内容如下：

问题

早期使用二甲双胍是否能改善妊娠期糖尿病患者的血糖控制并减少胰岛素的使用？

调查结果

在这项随机临床试验中，开始注射胰岛素和在妊娠32周或38周空腹血糖水平为5.1 mmol/L（92 mg/DL）或更高的复合结果在两组之间没有显著差异。

意义

大小的次要转归较低。母亲和新生儿的发病率没有差异。早期开始使用二甲双胍并不能降低妊娠32周或38周空腹血糖水平为5.1 mmol/L或更高或开始使用胰岛素的发生率。当使用二甲双胍时，应继续对小于胎龄率进行持续审查。

摘要内容如下：

重要性

妊娠期糖尿病是一种常见的妊娠并发症，其最佳治疗方法尚不确定。测试在妊娠32周或38周时，早期使用二甲双胍是否会减少胰岛素的使用或改善空腹高血糖。

研究设计和参与者

在爱尔兰的两个中心（一家三级医院和一家较小的地区医院）进行的双盲、安慰剂对照试验。参与者从2017年6月至2022年9月入组，并随访至产后12周。参与者包括510名根据世界卫生组织2013年标准诊断为妊娠糖尿病的个体（535名孕妇）。

干预措施

除常规治疗外，按1:1随机分配至安慰剂组或二甲双胍组（最大剂量，2500 mg）。

主要结局和措施

主要转归是在妊娠32周或38周开始使用胰岛素或空腹血糖水平为5.1 mmol/L或更高的复合转归。

结果

在510名参与者（平均年龄34.3岁）中，535名孕妇被随机分组。主要复合结局在两组间无显著差异，二甲双胍组150例妊娠（56.8%），安慰剂组167例妊娠（63.7%）（组间差异，-6.9%[95%CI，-15.1%至1.4%]；相对危险度，0.89[95%可信区间，0.78-1.02]；P=.13）。在6个预先指定的次要母体结局中，3个有利于二甲双胍组，包括开始使用胰岛素的时间、自我报告的毛细血管血糖控制和妊娠期体重增加。次要新生儿结局因组而异，二甲双胍组中较小的新生儿（较低的平均出生体重、体重>4 kg的较低比例、>90%百分位数的较低比例和较小的头顶-足跟长度）在新生儿重症监护需求、需要呼吸支持的呼吸窘迫、需要光疗的黄疸、主要先天性异常、新生儿低血糖或5分钟Apgar评分低于7的比例方面没有差异。

结论和相关性

二甲双胍早期治疗的复合主要转归并不优于安慰剂。预先指定的次要结果数据支持二甲双胍在大型临床试验中的进一步研究。

英文原文如下：

Key Points

Question Does early metformin initiation improve glycemic control and reduce insulin use in pregnant individuals with gestational diabetes?

Findings In this randomized clinical trial, the composite outcome of insulin initiation and a fasting glucose level of 5.1 mmol/L (92 mg/dL) or greater at gestation weeks 32 or 38 was not significantly different between groups. Secondary outcomes of maternal glycaemic control, weight gain, and infant size were lower in the metformin group. There was no difference in maternal or neonatal morbidities.

Meaning Early metformin initiation did not reduce the occurrence of the combination of a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38 or insulin initiation. Ongoing review of rates of small for gestational age should continue when using metformin.

Abstract

Importance Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain.

Objective To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38.

Design, Setting, and Participants Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks’ postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria.

Interventions Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care.

Main Outcomes And Measures The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38.

Results Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, −6.9% [95% CI, −15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7.

Conclusion and relevance Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials.

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