Some studies have raised concerns about a potential link between the widely used type 2 diabetes drug metformin and an increased risk of conceiving a baby with birth defects. However, new research suggests that the use of the medication among men planning to conceive or women in early pregnancy does not appear to be linked with an increased risk of major birth defects for their children.
The two studies, published Monday in the Annals of Internal Medicine, contradict a 2022 study that linked metformin use by men in the three months before conception to a 40% increased risk of birth defects in their offspring.
Assurance for Parents
The findings provide “assurance” for parents, said Dr. Ran Rotem, an author of the new study on the paternal use of metformin and a researcher at the Harvard T.H. Chan School of Public Health. “Conventionally and traditionally, the mother has been the focus when it comes to pregnancy and fetal health. What we are increasingly finding is that the father is also important,” he said. Rotem suggested that the increased risk seen in previous research could be associated with diabetes itself or related comorbidities, not the medication.
“When we think about a medication, we also have to think about the underlying conditions in which the medication is usually prescribed,” Rotem said. “We know that diabetes itself is tricky when it comes to both fertility and potential complications in pregnancy and in newborns.”
Study on Paternal Use
For the study on paternal use of metformin, researchers at Harvard and the Kahn-Sagol-Maccabi Research and Innovation Center in Israel analyzed data from birth and medical records of nearly 400,000 babies born in Israel between 1999 and 2020. They compared this data with information on the babies’ fathers, including their ages, laboratory test results, and medication records.
The researchers found that the prevalence of major birth defects was 4.7% in children of fathers not exposed to diabetes medications in the months leading up to conception, compared with 6.2% in children of fathers exposed to metformin before conceiving. However, after adjusting for factors such as the fathers’ underlying health conditions and whether the mother also had diabetes, they found no increased risk of major birth defects in children exposed to paternal metformin.
Impact of Maternal Use
The other study published in the Annals of Internal Medicine had similar findings for mothers. Researchers from Harvard T.H. Chan School of Public Health studied data on more than 12,000 women with type 2 diabetes and their pregnancies. The data showed that the estimated risk for giving birth to a baby with birth defects was about 6% when the mother received insulin plus metformin, versus 8% when the mother received insulin alone.
Dr. Yu-Han Chiu, the lead author of the study, noted, “Poor blood sugar control is a risk factor for birth defects. Insulin in combination with metformin may result in better blood sugar control than using insulin alone.”
Expert Opinions
Dr. Meleen Chuang, medical director of women’s health at the Family Health Centers at NYU Langone, said the new studies are “well done” and would not change the way metformin is prescribed for parents trying to conceive. She emphasized the importance of weight loss, diet, and exercise as part of preconception care for both parents.
Dr. Sarah Martins da Silva of the University of Dundee, in an editorial published alongside the studies, called the risks associated with metformin a “complex picture.” However, she noted that the new studies suggest metformin is a safe and effective treatment option for men and women trying to conceive and for managing hyperglycemia in pregnant women in the first trimester.
Overall, the findings suggest that maintaining good cardiometabolic health is crucial for both partners and that metformin remains a viable and safe option for managing type 2 diabetes in those planning to conceive.
