Rowan Janet A, Hague William M, Gao Wanzhen, Battin Malcolm R, Moore M Peter
National Women's Health, Auckland City Hospital, Grafton, Auckland, New Zealand.
N Engl J Med. 2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193.
Metformin is a logical treatment for women with gestational diabetes mellitus, but randomized trials to assess the efficacy and safety of its use for this condition are lacking.
We randomly assigned 751 women with gestational diabetes mellitus at 20 to 33 weeks of gestation to open treatment with metformin (with supplemental insulin if required) or insulin. The primary outcome was a composite of neonatal hypoglycemia, respiratory distress, need for phototherapy, birth trauma, 5-minute Apgar score less than 7, or prematurity. The trial was designed to rule out a 33% increase (from 30% to 40%) in this composite outcome in infants of women treated with metformin as compared with those treated with insulin. Secondary outcomes included neonatal anthropometric measurements, maternal glycemic control, maternal hypertensive complications, postpartum glucose tolerance, and acceptability of treatment.
Of the 363 women assigned to metformin, 92.6% continued to receive metformin until delivery and 46.3% received supplemental insulin. The rate of the primary composite outcome was 32.0% in the group assigned to metformin and 32.2% in the insulin group (relative risk, 0.99 [corrected]; 95% confidence interval, 0.80 [corrected] to 1.23 [corrected]). More women in the metformin group than in the insulin group stated that they would choose to receive their assigned treatment again (76.6% vs. 27.2%, P<0.001). The rates of other secondary outcomes did not differ significantly between the groups. There were no serious adverse events associated with the use of metformin.
In women with gestational diabetes mellitus, metformin (alone or with supplemental insulin) is not associated with increased perinatal complications as compared with insulin. The women preferred metformin to insulin treatment. (Australian New Zealand Clinical Trials Registry number, 12605000311651.).
二甲双胍是治疗妊娠期糖尿病女性的合理药物，但缺乏评估其用于该病症疗效和安全性的随机试验。
我们将751例妊娠20至33周的妊娠期糖尿病女性随机分配接受二甲双胍开放治疗（必要时补充胰岛素）或胰岛素治疗。主要结局是新生儿低血糖、呼吸窘迫、光疗需求、出生创伤、5分钟阿氏评分低于7分或早产的综合情况。该试验旨在排除与接受胰岛素治疗的女性相比，接受二甲双胍治疗的女性所生婴儿的这一综合结局增加33%（从30%增至40%）的情况。次要结局包括新生儿人体测量指标、母体血糖控制、母体高血压并发症、产后糖耐量以及治疗的可接受性。
在分配接受二甲双胍治疗的363例女性中，92.6%持续接受二甲双胍治疗直至分娩，46.3%接受了补充胰岛素治疗。二甲双胍组主要综合结局发生率为32.0%，胰岛素组为32.2%（相对风险，0.99[校正后]；95%置信区间，0.80[校正后]至1.23[校正后]）。二甲双胍组表示会再次选择接受分配治疗的女性多于胰岛素组（76.6%对27.2%，P<0.001）。两组间其他次要结局发生率无显著差异。使用二甲双胍未出现严重不良事件。
对于妊娠期糖尿病女性，与胰岛素相比，二甲双胍（单独使用或联合补充胰岛素）不会增加围产期并发症。女性更倾向于二甲双胍而非胰岛素治疗。（澳大利亚和新西兰临床试验注册号，12605000311651。）
