The risk of pre-eclampsia in women taking metformin: systematic review and meta-analysis

Abdelrahim Alqudah, Michelle McKinley, Ross McNally, Una Graham, Chris Watson, Timothy Lyons, Lana McClements

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42 Citations (Scopus)
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AIMS Hypertensive disorders in pregnancy, particularly pre-eclampsia, are the leading cause of maternal or foetal morbidity and mortality, and effective treatments are lacking. The aim of this study was 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.

Medline, EMBASE, Web of Science and Scopus databases were searched. Both randomised controlled trials (RCTs) and prospective observational cohort studies (CSs) 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 RCTs comparing metformin treatment (n=611) to placebo/control (n=609), no difference in the risk of pre-eclampsia was demonstrated (combined/pooled RR=0.86; 95% CI 0.33-2.26; p=0.76; I2=66%). Meta-analysis of four CSs again showed no significant effect (RR=1.21; 95% CI 0.56-2.61; p=0.62; I2=30%). However, a meta-analysis of eight RCTs comparing metformin (n=838) to insulin (n=836) showed reduced risk of pre-eclampsia with metformin (RR=0.68; 95% CI 0.48-0.95; p=0.02; I2=0%). No heterogeneity was present in the metformin vs. insulin analysis of RCTs, whereas high levels of heterogeneity were present in studies comparing metformin to placebo/control. Pre-eclampsia was a secondary outcome in most of the studies. Mean weight gain from enrolment to delivery was lower in the metformin group (p=0.05, metformin vs. placebo; p=0.004, metformin vs. insulin).

In studies randomising pregnant women to glucose-lowering therapy, metformin is associated with smaller gestational weight gain and a lower risk of pre-eclampsia than insulin.

Original languageEnglish
Pages (from-to)160-172
Number of pages13
JournalDiabetic Medicine
Issue number2
Early online date14 Jan 2018
Publication statusPublished - Feb 2018


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