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Some studies have raised concerns about a potential link between metformin, a widely used type 2 diabetes medication, and an increased risk of conceiving a baby with birth defects. But new research now suggests that use of the drug in men planning to conceive or in women early in pregnancy does not appear to be linked to an increased risk of major birth defects for their children.
The two studies, published Monday in Annals of Internal Medicine, contradict a 2022 study that linked metformin use by men in the three months before conceiving a baby with a 40% increased risk of birth defects in their offspring.
The findings provide “reassurance” to parents, said Dr. Ran Rotem, author of the new study on paternal metformin use and a researcher at the Harvard TH Chan School of Public Health.
“Traditionally, the mother is the center of attention when it comes to pregnancy, fetal health and newborn health. What we are seeing more and more is that the father is also important,” he said.
He added that the increased risk of birth defects observed in previous research might be associated with diabetes disease or associated comorbidities, and not so much with the medication itself.
“When we think about a drug, we also need to think about the underlying conditions for which the drug is usually prescribed,” Rotem said. “We know that diabetes itself is tricky in terms of fertility and potential complications during pregnancy and in newborns. »
Metformin is a first-line medication in the treatment of type 2 diabetes and has been widely used to help control blood sugar levels since the 1960s.
This medication is now the most commonly prescribed oral medication for type 2 diabetes, and before taking metformin, it is recommended that people tell their doctor if they are planning to become pregnant, are pregnant, or are are breastfeeding.
For the study on paternal use of metformin, researchers from the Harvard TH Chan School of Public Health and the Kahn-Sagol-Maccabi Research and Innovation Center at Maccabi Healthcare Services in Israel analyzed data from birth certificates and medical records of nearly 400,000 babies born in Israel. Israel between 1999 and 2020.
They compared this data with information about the babies’ fathers, such as their ages, laboratory test results and medication records, including data on metformin prescriptions.
Although the researchers didn’t specifically look at how long the men had been taking the drug, “we had many people who had been taking the drug for a long time, and the results were pretty consistent for those people as well,” Rotem said. said.
Researchers found that the prevalence of major birth defects was 4.7% among children of fathers not exposed to diabetes medications in the months before conception, compared to 6.2% among children of fathers exposed to metformin before conceiving.
When the researchers adjusted their data for factors such as the father’s other underlying health conditions and whether the mother also had diabetes or related comorbidities, they found no increased risk of major birth defects among the children exposed to paternal metformin.
Men who used diabetes medications during the period of sperm development, preceding conception, tended to be older, had a higher prevalence of underlying health conditions, and were more likely to have fertility problems. fertility and smoking history than fathers not exposed to these drugs. diabetes medications.
“We find that paternal use of metformin during the period of sperm development is not associated with an excess risk of malformation in newborns, providing evidence that fathers planning to start a family can continue to use this medication to control their diabetes,” Rotem said. “More broadly, our study also suggests that maintaining a good cardiometabolic health profile is important for both partners. »
A higher prevalence of underlying health conditions as well as fertility problems was also observed among mothers of children whose fathers used metformin, compared to mothers of children without paternal exposure to anti-metformin medications. diabetes.
“If the father is taking diabetes medications, the mother is much more likely to also be taking diabetes medications or have other metabolic comorbidities,” Rotem said.
“We know that diabetes itself is not good when it affects the mother, and we have discovered that it is also difficult for fathers,” he said. “If you can manage your diabetes by simply changing your lifestyle – exercising more, watching your diet – that’s probably a good thing, and it’s helpful either way. But if you must take medication, it appears that metformin is a safe choice for both. »
The data also showed that the risk of birth defects was higher when the father took metformin with other medications, described as combination therapy. Paternal use of metformin alone, known as monotherapy, does not appear to increase the risk of birth defects.
“When we looked at specific treatment regimens, slightly elevated additional risks were observed, particularly in children of fathers using metformin in combination with other diabetes medications,” Rotem said.
“But we also observed that fathers who took multiple medications had more poorly controlled diabetes,” he said. “This again indicates that the slightly elevated risk observed for diabetes combination therapies was likely not caused by the drugs themselves, but rather by the fathers’ worse cardiometabolic health profile.”
The other study published Monday in Annals of Internal Medicine found somewhat similar results for mothers. According to the study, women who continued to use metformin and added insulin as treatment during their first trimester of pregnancy showed little or no increased risk of giving birth to a baby with major birth defects. compared to women who stopped metformin and switched to insulin.
The researchers, also from the Harvard TH Chan School of Public Health, studied data from more than 12,000 women with type 2 diabetes and their pregnancies. Data comes from the U.S. Health Care Administration Medicaid database from 2000 to 2018.
The analysis showed that the estimated risk of giving birth to a baby with birth defects was about 6% when the mother received insulin plus metformin, compared to 8% when the mother received insulin alone. .
“We were not surprised by our findings. Although metformin can cross the placental barrier, potentially affecting the fetus, metformin may help control blood sugar, which may reduce the risk of birth defects,” Dr. Yu-Han Chiu, lead author of the study and researcher at Harvard TH Chan. School of Public Health and Penn State College of Medicine, said in an email.
“Poor blood sugar control is a risk factor for birth defects. Insulin in combination with metformin may result in better blood sugar control than insulin alone. This may explain why we observed a slightly lower risk of live birth with birth defects compared to using insulin alone,” Chiu said. “For women with type 2 diabetes who are currently taking metformin and planning to conceive, our study suggests that continuing metformin results in no or little increased risk of birth defects compared to switching to metformin. ‘insulin.”
Both new studies are “well done,” Dr. Meleen Chuang, medical director of women’s health at NYU Langone Family Health Centers, said in an email.
“I wouldn’t change the way metformin is prescribed to parents trying to conceive,” said Chuang, who was not involved in the new studies and is chief of obstetrics and gynecology at NYU Langone Brooklyn.
“I would encourage weight loss, diet and exercise as part of both parents’ preconception care,” she added. “Reducing modifiable risk factors such as weight loss, smoking, alcohol and substance use are some ways to improve health and fertility.”
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The possible risks that may arise from paternal and maternal use of metformin remain a “complex picture”, but the new studies are helping to clarify this evolving picture, wrote Dr Sarah Martins da Silva, of the University of Dundee in United Kingdom. in an editorial published Monday alongside the two studies.
“Clearly, individual risks and benefits should be carefully considered and results should be interpreted with caution since studies lack information on glycemic control,” she wrote.
“Nevertheless, these recent analyzes suggest that metformin is a safe and effective treatment option for (type 2 diabetes) in men and women trying to conceive as well as for managing high blood sugar in pregnant women during pregnancy. first trimester,” she added, “and it might be time to reconsider current prenatal care guidelines that advocate a switch to insulin therapy.