Preeclampsia is a morbidity and mortality risk for both mother and the unborn baby. There is only one drug – aspirin - which prevents preeclampsia (relative risk reduction of only 18%). And once diagnosed, there are no drugs that can slow disease progression.
Metformin is currently used for glycaemic control in gestational diabetes. In bench to bedside studies, our team has discovered metformin may have the ability to quench disease severity in those diagnosed with preeclampsia.
The Translational Obstetrics Group set up a laboratory drug screening pipeline which utilises multiple assays and tests drugs for their ability to 1) decrease placental release of sFlt-1 and other anti-angiogenic factors, and 2) decrease endothelial dysfunction in maternal blood vessels (1 and 2 are thought to be central to the pathogenesis of preeclampsia).
Using our laboratory drug screening pipeline, we reported metformin may be a promising drug to treat or prevent preeclampsia (Brownfoot et al AMJOG 2016).
We translated this idea to the clinic and have just completed a large trial in South Africa (PI2 Trial). We randomised 180 participants with preterm preeclampsia (26-32 weeks gestation) to placebo or 3 grams of oral metformin. Those in the metformin arm had a prolong pregnancy of 7.6 days (primary outcome). Importantly, there was a reduced length of neonatal admission post birth (which may reflect better health at birth). We are now implementing The PI3 Trial, which will randomise 500 participants. If our findings are validated, metformin may be the first disease modifying drug for preeclampsia. The potential for clinical impact is significant.