Metformin decreased toxin levels implicated in preeclampsia, while also helping to heal injured omental blood vessels, researchers in Australia have reported.
Since the drug, a common treatment for type 2 diabetes, is already proven safe during pregnancy, the study’s lead author Dr. Fiona Brownfoot said clinical trials to test metformin’s efficacy in preventing and treating preeclampsia are “justified”. The findings were published online Dec. 22 in the American Journal of Obstetrics and Gynecology (doi: 10.1016/j.ajog.2015.12.019).
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Preeclampsia is characterized by elevated levels of soluble vascular endothelial growth factor receptor 1 and soluble endoglin, toxins produced by the placenta. When elevated, these toxins tend to damage endothelial cells, manifesting clinically as hypertension and multisystem organ injury. Preeclampsia occurs in 5%-8% of pregnancies, presenting after week 20 of gestation with new-onset hypertension and proteinuria. Since there have been no agents or drugs to decrease the production of these toxins in pregnancy, the only treatment options for preeclampsia are expectant management and delivery.
Dr. Brownfoot, a researcher in the Translational Obstetrics Group in the department of obstetrics and gynecology at the University of Melbourne and her associates found that when endothelial and placental cells taken from 23 women diagnosed with severe preterm proteinuric preeclampsia were incubated with metformin, there were improvements in endothelial dysfunction when compared with 25 gestationally matched controls. Metformin was also shown to improve whole blood vessel angiogenesis impaired by elevated toxin levels.
“Metformin appears to be the aspirin of the 21st century,” Dr. Roberto Romero, editor-in-chief of the American Journal of Obstetrics and Gynecology, said in a statement.
Noting metformin’s use in diabetes as well as in polycystic ovarian disease, and its recently discovered anticancer properties, Dr. Romero said the recent findings are “exciting and promising,” particularly since antiangiogenesis occurs not only in preeclampsia, but in other pregnancy complications such as fetal death, fetal growth restriction, and premature labor. He called for systematic reviews of previous randomized clinical trials of metformin in pregnant women, as well as new randomized studies to determine the effectiveness of metformin in preventing preeclampsia.
The work was funded by the National Health and Medical Research Council of Australia. The researchers reported having no conflicts of interest.
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