Taking Diabetes Drug Metformin While Pregnant May Impact Child’s Brain Development

NUTHETAL, Germany — Metformin is one of the most common and wildly used drugs by people with diabetes and prediabetes. However, a concerning new study finds taking metformin during pregnancy may impact the child’s long-term brain development.

German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE) researchers delved deep into the effects of metformin, an antidiabetic medication that is increasingly being prescribed to pregnant women with gestational diabetes. Gestational diabetes affects about one in six pregnant women globally, posing significant risks not only to the mothers but also to their unborn children.

According to the American Diabetes Association, up to 10 percent of pregnancies in the United States are affected by gestational diabetes yearly. This condition can lead to severe consequences, including a heightened likelihood of the mother developing Type 2 diabetes later in life and the child facing an increased risk of metabolic disorders and obesity.

Metformin, an oral medication that lowers blood sugar levels by reducing glucose production in the liver and boosting insulin sensitivity in cells, has been a beacon of hope for many. It can cross the placenta, potentially impacting the fetus. While it’s known for its efficacy in adults, the implications of its placental passage during pregnancy, particularly on the offspring’s brain development, have remained largely uncharted territory.

Metformin

The study, published in the journal Molecular Metabolism, explored whether metformin benefits extend to the offspring and if it causes long-term physiological changes, especially concerning the development of neuronal circuits in the hypothalamus. The hypothalamus plays a critical role in energy balance, influencing hunger, thirst, and the body’s energy expenditure.

Utilizing mice to mimic severe obesity before pregnancy and excessive weight gain during pregnancy, the researchers simulated conditions of gestational diabetes. They treated pregnant mice with insulin, metformin, or a placebo during what would correspond to be the third trimester of a human pregnancy in terms of brain development. This study phase was crucial for examining metformin’s effects on early postnatal development.

Their findings revealed that while metformin had positive effects on pregnant mice, it did not benefit the offspring in the same way.

“As a result of antidiabetic treatment in the early postnatal period, we were able to identify alterations in the weight gain and hormonal status of the offspring, which were critically dependent on the metabolic state of the mother,” says study author Dr. Rachel Lippert, junior research group leader at DIfE, in a media release.

The study also observed sex-specific changes in the hypothalamus signaling pathways of the mice, linked to energy regulation, which were affected by metformin exposure.

“Given the increasing prevalence, education about gestational diabetes and preventive measures are of vital importance. If we can find a way to manage lifestyle and diet more proactively, we are in a better position to exploit the potential of gestational diabetes treatment,” notes Dr. Lippert.

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