Two new studies offer reassurance that using the diabetes drug metformin before and during pregnancy is not linked to birth defects.

The latest findings, which apply to men planning to conceive with their partners or women in early pregnancy, contradict a 2022 study that found metformin use by men in the three months before they conceived a baby was associated with a 40% increased risk of birth defects in their children.

“Conventionally and traditionally, the mother has been the focus when it comes to pregnancy and when it comes to fetal health and the health of the newborn. What we are increasingly finding is that the father is also important,” Dr. Ran Rotem, who authored the new study on the paternal use of metformin and birth defects, told CNN.

“We know that diabetes itself is not good when it is in the mother, and we are finding evidence that it’s also tricky for the fathers,” Rotem noted. “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.”

The raised risk of birth defects seen in earlier research could have been associated with diabetes itself or with related illnesses, instead of the medication, noted Rotem, a researcher at the Harvard T.H. Chan School of Public Health in Boston.

“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.”

In Rotem’s study, his team analyzed data from medical records on nearly 400,000 babies born in Israel between 1999 and 2020. They compared that with information on the babies’ fathers, such as their ages, lab test results and medication records.

His team found the rate 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.

But when the researchers also weighed fathers’ other underlying health conditions and whether the mother also had diabetes or related co-morbidities, they found no increased risk of major birth defects in children exposed to paternal metformin.

The data did show that the risk of a birth defect was higher when the father used other medications along with metformin.

“When we examined specific treatment regimens, modestly elevated excess risks were still observed, specifically among children of fathers who used metformin in tandem with some other diabetes medication,” Rotem said.

“But we also observed that fathers who took multiple medications had more poorly controlled diabetes,” he added. “This again indicates that the modestly elevated risk seen for diabetes polytherapies was likely not caused by the medications themselves, but rather by the worse cardio-metabolic health profile of the fathers.”

The second study, published Tuesday in the Annals of Internal Medicine alongside Rotem’s research, reported similar findings for women. Those who continued using metformin while adding insulin as a treatment in their first trimester of pregnancy showed little to no increased risk of giving birth to a baby with birth defects.

Those researchers, also from Harvard T.H. Chan School of Public Health, studied Medicaid data on more than 12,000 women with type 2 diabetes and their pregnancies.

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.

“We were not surprised by our findings. Although metformin may cross the placenta, potentially affecting the fetus, metformin can help with blood sugar control which may lower the risk of birth defects,” study author Dr. Yu-Han Chiu, a researcher at the Harvard T.H. Chan School of Public Health and Penn State College of Medicine, told CNN.

“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.

The new studies begin to clarify the risks of metformin use around pregnancy by both parents, Dr. Sarah Martins da Silva, of the University of Dundee in Scotland, wrote in an editorial published with the studies.

“Nonetheless, these recent analyses suggest that metformin is a safe and effective treatment option for [type 2 diabetes] for men and women trying to conceive as well as managing hyperglycemia [high blood sugar] in pregnant women in the first trimester, and it may be time to reconsider current prenatal care guidelines that advocate switching to insulin therapy,” she added.

More information

The American Diabetes Association has more on diabetes and pregnancy.

SOURCE: Annals of Internal Medicine, June 18, 2024; CNN

Source: HealthDay

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