Metformin: is it safe during pregnancy?
Metformin is an oral medication that has been prescribed to treat type 2 diabetes for 60 years. For more than 40 years, it has been used during pregnancy. However, the question of whether metformin should be taken during the later months of pregnancy is a subject of ongoing debate. That’s because the long-term effects on the fetus are not known.
Women may take metformin during pregnancy for a variety of reasons: before becoming pregnant to treat type 2 diabetes, to treat infertility issues caused by polycystic ovary syndrome (PCOS), or to control gestational diabetes.
“Very early in pregnancy, approximately the first 10 weeks, unhealthy blood glucose levels can cause birth defects, so we want to keep blood glucose levels as close to normal range as possible so malformations don’t occur,” says Mary R. Loeken, Ph.D., Research Investigator, Section on Islet Cell and Regenerative Biology at Joslin Diabetes Center. “This window of time is when the organ systems are forming and the embryo is susceptible to malformations.”
On the other hand, high blood glucose levels later in pregnancy can cause complications for the mother, such as hypertension or preeclampsia, and impact the birth weight of the baby.
In a scientific review published in the September issue of Diabetologia, Dr. Loeken reviewed what is known about the effects of metformin used at different stages of pregnancy on the embryo or fetus. As a basic science researcher, her aim is to understand the molecular and cellular processes of metformin at the different stages of prenatal development.
She explained that metformin turns on an enzyme known as AMP-activated protein kinase (AMPK), altering cellular activity. In mouse models, this AMPK activity contributes to congenital malformations. Thus, the question that often gets asked is: Does taking metformin early in pregnancy put the embryo at risk of malformations?
Her previous research revealed that the answer to this question is “no”. The reason: Molecules known as “transporters” are needed to carry metformin into the cells where it can act on AMPK. But at the embryonic stage, when malformations can occur, these transporter molecules don’t even exist.
“There is no channel for getting metformin into embryonic cells. During this stage, the embryo’s cells are so immature that metformin just can’t get into them so it’s not likely to do anything,” says Dr. Loeken. “Our work suggests that there is no effect on the embryo if the mother becomes pregnant while she’s on metformin.”
However, even though metformin is widely used for gestational diabetes, its use in the second and third trimesters of pregnancy remains controversial. What is behind the cause for concern?