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).
Following were the key findings of the study:
- Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (n=76) days compared with 7.9 (n=74) days in the placebo arm, a median difference of 9.6 days.
- Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (n=40) days compared with 4.8 (n=61) days in the placebo arm, a median difference of 11.5 days.
- Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ.
- In the metformin arm, birth weight increased non-significantly, and length of stay decreased in the neonatal nursery.
- No serious adverse events related to trial drugs were observed, although diarrhea was more common in the metformin arm.
"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
