Is metformin protective?
Question: “I was on Metformin when I conceived but the midwife I was seeing early in the pregnancy took me off the Metformin after the first trimester. The doctor I was seeing later in the pregnancy said he would have kept me on it, but since I was off it, left me off. Would it have made a difference?” Answer: No one knows, yet, if there will be a therapeutic use for metformin in preeclampsia, and no one can say for certain what would have happened to you. There are some reasons to think metformin, used differently from how it is used in polycystic ovarian syndrome (PCOS) or diabetes, might lower risk of preeclampsia, and some reasons to think it might not have much effect. Some women on metformin for PCOS or gestational diabetes have gone on to develop preeclampsia, so we know that the standard way of using metformin will not prevent all cases. The hope is that it might be able to be used in a more targeted way to lower individual risk of preeclampsia. It does not increase miscarriage risk when continued during pregnancy, but we are still learning what this drug does in pregnancy. Trials into metformin for preeclampsia risk reduction have been started, but they have not finished yet and we do not know what they will find. The Preeclampsia Foundation is funding a trial that is investigating this question. When women with obesity have continued to take metformin during pregnancy, their rates of preeclampsia did not change when compared to women like them who were not taking metformin. When women with PCOS were given metformin starting in the late first trimester, their rates of preeclampsia did not change. But meta-analyses of this data have suggested that there may still be a benefit. This is very similar to what happened in early aspirin research, so it may be that there is still a benefit in a subpopulation and the trials are not large enough to reliably detect that effect. Perhaps we can start metformin at a different time, or with a different dosage, and then there will be a lowering of risk.
We do know from research into the effects of metformin on placental tissue - this is work done in petri dishes - that metformin affects the production of two forms of proteins (sFLT and sENG) that circulate in the bloodstream and that cause some preeclampsia symptoms. If it can be used to lower the levels of those proteins, then it ought to lower preeclampsia risk in some women, or slow its progression in some women. But this research must be translated from research bench to patient bedside before it can change our care.
For a technical overview of metformin’s potential, see here. To find your individual risk and discuss the potential for metformin use in your case, you may want to see a maternal-fetal medicine specialist or an obstetric medicine specialist prior to any future pregnancy.