Metformin, common diabetes drug, not linked to increased birth defect risk

close up of pregnant woman holding glucose meter and checking blood sugar level by herself at home. gestational diabetes concept.

June 26, 2024—Infants born to men or to women taking metformin, a common drug used to manage type 2 diabetes, do not appear to be at higher risk of birth defects, according to two new studies led by researchers at Harvard T.H. Chan School of Public Health.

Both studies were published June 18 in the Annals of Internal Medicine. Ran Rotem, research associate in the Department of Environmental Health, led the study on paternal use of metformin. Yu-Han Chiu, former postdoctoral fellow and research scientist in the Harvard Chan Department of Epidemiology’s CAUSALab, and currently an assistant professor in Penn State College of Medicine’s Division of Epidemiology, led the study on maternal use.

Previous research found an association between paternal use of metformin and birth defects. To further investigate this topic, the researchers observed the health outcomes of nearly 384,000 infants born in Israel between 1999 and 2020 and the health records of their fathers. The new study found that the prevalence of birth defects among infants whose fathers took metformin leading up to conception was 6.2%, compared to 4.7% among infants whose fathers did not take metformin. After adjusting for other relevant health factors, such as fathers’ and mothers’ other health conditions, the researchers concluded that metformin did not elevate infants’ risk of birth defects.

Meanwhile, research on maternal use of metformin during early pregnancy has been limited. To expand the evidence base, the researchers used Medicaid data on nearly 12,500 pregnant women in the U.S. with diabetes to estimate how the risk of birth defects was impacted by two treatments: insulin or a combination of insulin and metformin. Similar to the study on paternal use of metformin, this study found that maternal use didn’t appear to pose a risk. The researchers estimated that, for a woman with diabetes, the risk of giving birth to an infant with birth defects was 5.7% when taking insulin and metformin and 8% when taking insulin alone.

“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. This may explain why we observed a slightly lower risk of live birth with congenital malformations when comparing with using insulin alone,” Chiu said in a June 17 CNN article about the studies.

According to the researchers, the higher prevalence of birth defects among infants born to parents with diabetes, which was found in previous research, may be due to parents’ worse cardiometabolic health, rather than any medication treating them.

“When we think about a medication, we also have to think about the underlying conditions in which the medication is usually prescribed,” Rotem told CNN. “We know that diabetes itself is tricky when it comes to both fertility and potential complications in pregnancy and in newborns.”

He added, “If you can manage diabetes with just changing your lifestyle—doing more exercise, watching your diet—that’s probably good, and that’s helpful anyways. But if you have to be medicated, it seems like metformin is a safe choice for both [mothers and fathers].”

Read the CNN article: Use of popular diabetes drug in preconception or early pregnancy may not be tied to higher birth defect risk, studies suggest

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