Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, UK.
Diabet Med. 2018 Feb;35(2):160-172. doi: 10.1111/dme.13523.
To perform meta-analyses of studies evaluating the risk of pre-eclampsia in high-risk insulin-resistant women taking metformin prior to, or during pregnancy.
A search was conducted of the Medline, EMBASE, Web of Science and Scopus databases. Both randomized controlled trials and prospective observational cohort studies of metformin treatment vs. placebo/control or insulin either prior to or during pregnancy were selected. The main outcome measure was the incidence of pre-eclampsia in each treatment group.
Overall, in five randomized controlled trials comparing metformin treatment (n = 611) with placebo/control (n = 609), no difference in the risk of pre-eclampsia was found [combined/pooled risk ratio (RR), 0.86 (95% CI 0.33-2.26); P = 0.76; I = 66%]. Meta-analysis of four cohort studies again showed no significant effect [RR, 1.21 (95% CI 0.56-2.61); P = 0.62; I = 30%]. A meta-analysis of eight randomized controlled trials comparing metformin (n = 838) with insulin (n = 836), however, showed a reduced risk of pre-eclampsia with metformin [RR, 0.68 (95% CI 0.48-0.95); P = 0.02; I = 0%]. No heterogeneity was present in the metformin vs. insulin analysis of randomized controlled trials, whereas high levels of heterogeneity were present in studies comparing metformin with placebo/control. Pre-eclampsia was a secondary outcome in most of the studies. The mean weight gain from time of enrolment to delivery was lower in the metformin group (P = 0.05, metformin vs. placebo; P = 0.004, metformin vs. insulin).
In studies randomizing pregnant women to glucose-lowering therapy, metformin was associated with lower gestational weight gain and a lower risk of pre-eclampsia compared with insulin.
对评估有胰岛素抵抗高风险的女性在怀孕前或怀孕期间服用二甲双胍后发生子痫前期风险的研究进行荟萃分析。
检索了 Medline、EMBASE、Web of Science 和 Scopus 数据库。选择了二甲双胍治疗与安慰剂/对照或胰岛素治疗的随机对照试验和前瞻性观察队列研究。主要观察指标是每个治疗组子痫前期的发生率。
总体而言，在五项比较二甲双胍治疗（n=611）与安慰剂/对照（n=609）的随机对照试验中，子痫前期的风险无差异[合并/汇总风险比（RR），0.86（95%置信区间 0.33-2.26）；P=0.76；I²=66%]。四项队列研究的荟萃分析也未显示出显著效果[RR，1.21（95%置信区间 0.56-2.61）；P=0.62；I²=30%]。然而，对 8 项比较二甲双胍（n=838）与胰岛素（n=836）的随机对照试验的荟萃分析显示，二甲双胍降低了子痫前期的风险[RR，0.68（95%置信区间 0.48-0.95）；P=0.02；I²=0%]。在比较二甲双胍与胰岛素的随机对照试验分析中，不存在异质性，而在比较二甲双胍与安慰剂/对照的研究中，存在高度异质性。子痫前期是大多数研究的次要结局。二甲双胍组从登记到分娩的体重增加平均值较低（P=0.05，二甲双胍与安慰剂；P=0.004，二甲双胍与胰岛素）。
在随机分配孕妇进行降糖治疗的研究中，与胰岛素相比，二甲双胍与较低的妊娠体重增加和子痫前期风险相关。
