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.
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Supervisor: Grieve, D. (Supervisor), Lyons, T. (Supervisor) & McClements, L. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy