4 years ago

Risk of pre-eclampsia in women taking metformin: a systematic review and meta-analysis

R. McNally, T. J. Lyons, L. McClements, U. Graham, A. Alqudah, C. J. Watson, M. C. McKinley
Aims 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. Methods 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. Results 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 0.86, 95% CI 0.33–2.26; P=0.76; I2=66%). Meta-analysis of four cohort studies again showed no significant effect (risk ratio 1.21, 95% CI 0.56–2.61; P=0.62; I2=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 (risk ratio 0.68, 95% CI 0.48–0.95; P = 0.02; I2=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). Conclusions 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. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/dme.13523

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