Metformin for prevention of pre-eclampsia in pregnant women: systematic review and meta-analysis

Introduction: Pre-eclampsia complicates 2-4% of pregnancies. Metformin is a promising therapeutic candidate as would reduce the secretion of soluble fms-like tyrosine kinase 1 and soluble endoglin from endothelial cells and primary villous trophoblasts. Objective: The objective of the study was to determine the effects and safety of metformin for preventing pre-eclampsia. Materials and methods: A systematic review was carried out with Cochrane methodology, performing an electronic search for randomized clinical trials in pregnant women, which compared the use of metformin with placebo or no intervention, and reported incidence of pre-eclampsia within their results. Review manager software was used for the statistical analysis. Results: Five studies were included with results for 1977 participants. A 56% reduction in the risk of pre-eclampsia in pregnant women who received metformin was found, compared to placebo or no intervention (RR 0.44; 95% confidence interval 0.21-0.90; random effects analysis; I² = 71%; Tau² = 0.46; low-quality evidence). No significant differences were found for the secondary outcomes. Conclusions: The use of metformin in overweight or obese pregnant women, beginning before 20 weeks of gestation, could reduce the risk of pre-eclampsia by 56%; however, the beneficial effect could be non-significant, due to heterogeneity and low quality of current evidence.