Research Shows Metformin Influences Fetal Brain Development

Metformin, the increasingly popular type 2 diabetes drug, has also gained favor as a treatment for gestational diabetes, too. And while it works wonders for the mothers, it might pose a possible threat to the offspring in the process.

A cross-sectional team of researchers operating out of the German Institute for Nutritional Research Potsdam-Rehbrücke (DIfE) has published new research that suggests metformin could threaten fetal brain development. The journal Molecular Metabolism published the study results in its January issue.

Historical Research Remains Lacking

According to the Centers for Disease Control and Prevention (CDC), more than 8 percent of pregnant women who gave birth in 2021 contracted gestational diabetes. That’s a sharp jump from 6 percent in 2016. It’s worse worldwide, with the latest published data showing that global prevalence is closer to 15 percent.

These climbing numbers not only complicate childbirth, threatening mother and child but also pose longer-term risks to the child in the form of metabolic disorders and obesity.

The medical community has increasingly relied on antidiabetic metformin as a viable substitute for insulin. However few studies have delved into the lasting effects of the antidiabetic on offspring’s health. The only established certainty has been metformin’s impact on the AMPK signaling pathway, which regulates the connectivity of nerve cells during brain development.

As a result, the German researchers sought to answer a pair of critical questions:

• Is treatment with metformin only helpful for the mother?
• And does metformin treatment pose long-term negative physiological dangers in the offspring?

Working with Mice

To answer those questions, the researchers worked with two mouse models, to address the two leading causes gestational diabetes:

• Severe overweight of the mother before pregnancy.
• Excessive weight gain during pregnancy.

To get there, the researchers worked with two sets of mice, offering one group a high-fat diet and the other normal –  control – diet.

Subsequently, the scientists treated the female mice and their offspring during lactation, which parallels the final trimester of human pregnancy concerning fetal brain development.

The treatment included either insulin, metformin, or a placebo. The team then tracked the subjects’ weight gain (or loss), recorded  multiple metabolic parameters and hormones, and examined “the molecular signaling pathways in the hypothalamus.”

Metformin Moved Past the Placenta

“As a result of the antidiabetic treatment in the early postnatal phase, we were able to identify changes in weight gain and hormonal status of the offspring that were decisively dependent on the metabolic state of the mother,” one of the study’s authors and Junior Research Group Leader Rachel Lippert explained.

In addition, the study showed “gender-specific changes in hypothalamic AMPK signaling” due to metformin exposure.

Lippert added that gestational diabetes therapy could offer a better alternative moving forward. 

“In view of the increasing prevalence, education about gestational diabetes and preventive measures are crucial,” she said. “If we find a way to make the lifestyle and diet more proactive, we can better exploit the potential for treating gestational diabetes.”

Further Reading

Metformin for SGA-Induced Weight Gain

Diabetic medications and major congenital malformations

Safety Issues When Prescribing Metformin