Extended-release metformin can prolong gestation in preterm pre-eclampsia: BMJ

Findings from a trial suggest that extended-release metformin can prolong gestation in women having preterm preeclampsia. 

Australia: The study, published in the BMJ showed that among women with a diagnosis of preterm pre-eclampsia at <32 weeks' (+0 days) gestation, those who received extended-release metformin had a 7.6-day prolongation of gestation versus those who received placebo. The findings provide proof of concept that treatment of preterm pre-eclampsia is possible.

Pre-eclampsia is a leading cause of neonatal and maternal morbidity and mortality. Preterm preeclampsia is one of the most severe variants, affecting 0.5% of all pregnancies. It is associated with substantially more maternal and neonatal morbidity and mortality versus pre-eclampsia occurring at term gestation. Apart from delivery, there is no treatment for pre-eclampsia.

Preterm pre-eclampsia often leads to delivery for maternal indications that result in iatrogenic premature delivery and increase the risk of major neonatal disability and death, particularly in low and middle-income countries. The availability of a safe treatment that delayed the progression of preterm pre-eclampsia could result in delivery of the baby at a less preterm gestation. Efforts to find drugs that are safe to administer during pregnancy and can slow the progression of preterm pre-eclampsia have been unsuccessful.

Against the above background, Catherine A Cluver, Stellenbosch University, Tygerberg Hospital, Cape Town, South Africa, and colleagues aimed to evaluate whether extended-release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia in a randomized, double-blind, placebo-controlled trial set in a referral hospital in Cape Town, South Africa.

The study included 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks' gestation undergoing expectant management. 90 of them were randomized to receive extended-release metformin and 90 to placebo. They were randomized to receive either 3 g of oral extended-release metformin or placebo daily, in divided doses, until delivery. 

The median time from randomization to delivery was 17.7 days (n=89) in the metformin arm and 10.1 (n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39). 

"Based on the findings of this study, we are cautiously optimistic that extended-release metformin prolongs gestation in women with preterm preeclampsia," wrote the authors. "Further trials are, however, needed."

Reference:

The study titled, "Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial," is published in the BMJ. 

DOI: https://www.bmj.com/content/374/bmj.n2103