Adjunctive metformin offers no protection against pre-eclampsia

Among pregnant women with early gestational diabetes or pre-existing type 2 diabetes (T2D), using metformin in addition to insulin neither lowers the likelihood of preterm pre-eclampsia nor improves serum biomarkers associated with cardiovascular disease risk, according to a study.

Researchers conducted a secondary analysis of the MOMPOD* study, in which the effect of adding metformin to insulin treatment on composite neonatal outcome in singleton pregnancies with early gestational diabetes or T2D was evaluated. The women were randomly assigned to receive metformin 1,000 mg twice daily or placebo at 11–23 weeks of gestation until delivery.

Blood samples at 24–30 weeks of gestation were collected in a subset of women. Then, the samples were analysed to measure serum levels of soluble endoglin, apolipoprotein B, vascular cell adhesion molecule-1, soluble fms-like tyrosine kinase 1, placental growth factor, high-sensitivity C-reactive protein, adiponectin, and vascular endothelial growth factor.

The primary outcome of preterm pre-eclampsia (defined as pre-eclampsia requiring delivery before 37 weeks of gestation) occurred in 119 of 831 women (14.3 percent) overall, with no significant difference between the metformin and the placebo groups (62 of 415 [14.9 percent] vs 57 of 416 [13.7 percent]).

The secondary outcome of preterm pre-eclampsia requiring delivery before 34 weeks of gestation occurred in 22 women receiving metformin and in 15 of those receiving placebo (5.3 percent vs 3.6 percent).

Multivariable regression analysis showed that compared with placebo, metformin had no significant effect on the occurrence of pre-eclampsia requiring delivery before 37 weeks of gestation (adjusted odds ratio [aOR], 1.04, 95 percent confidence interval [CI], 0.70–1.56) or before 34 weeks (aOR, 1.43, 95 percent CI, 0.73–2.81).

Finally, serum biomarker levels were similar between the metformin and placebo groups.

*Medical Optimization of Management of Overt Type 2 Diabetes in Pregnancy