Are drugs like Ozempic safe in pregnancy?

• Between 1–2% of all pregnancies around the world are affected by pregestational diabetes.
• Pregestational diabetes is considered one of the most challenging medical complications during pregnancy, and it increases the pregnant person’s risk for several potential pregnancy complications.
• The number of people using GLP-1 receptor agonist medications for type 2 diabetes has increased over the last few years.
• Researchers from the Harvard T.H. Chan School of Public Health have now found that medications such as GLP-1 receptor agonists do not increase congenital malformation risk in pregnancy when compared to insulin therapy.
• Scientists believe the number of infants prenatally exposed to these drugs will continue to increase.

Between 1–2% of all pregnancies worldwide are affected by pregestational diabetes, where the pregnant individual already had diabetes before becoming pregnant.

Pregestational diabetes is considered one of the most challenging medical complications that can occur during pregnancy, as it requires constant management of the pregnant person’s diabetes.

The condition can also increase the risk for potential pregnancy complications, including birth defects, miscarriage, fetal growth restriction, premature labor, and preeclampsia.

Pregnant people with type 2 diabetes still need to take their diabetes medications. Over the past few years, the number of people with type 2 diabetes taking GLP-1 receptor agonist medications like Ozempic and Trulicity has increased.

Now, new research from the Harvard T.H. Chan School of Public Health in Boston, MA, reports that the use of second-line noninsulin antidiabetic medications, such as GLP-1 receptor agonists, does not elevate the risk of major infant congenital malformations, when compared to insulin use.

Researchers also observed increased use of these antidiabetic medications throughout the 12-year study period. They believe this suggests the number of infants prenatally exposed to these drugs will continue to increase.

This study was recently published in the journal JAMA Internal Medicine.

Lack of data on effects of GLP-1 drugs in pregnancy

According to Dr. Sonia Hernández-Díaz, professor of epidemiology at Harvard T.H. Chan School of Public Health and senior author of this study, one of the most common medical complications in pregnancy is pregestational diabetes.

Outside of pregnancy, Dr. Hernández-Díaz told Medical News Today, noninsulin therapies for the treatment of type 2 diabetes — such as GLP-1 receptor agonists — have gained wide acceptance due to their efficacy and tolerability when compared to subcutaneous insulin injections.

“In pregnancy, these agents have potential benefits with respect to patient acceptability and adherence, and therefore improved glycemic control and pregnancy outcomes,” she told us. “However, the safety of these agents in pregnancy is largely unknown, as pregnant women are typically excluded from clinical trials; hence, treatment guidelines do not recommend these agents in pregnancy.”

“Thus, the lack of data on the safety of second-line noninsulin antidiabetic medications in the prenatal period has been a barrier to their use in pregnant women even when they may be beneficial, particularly for patients that don’t need or don’t tolerate insulin injections,” Dr. Hernández-Díaz noted.

Moreover, Dr. Hernández-Díaz pointed out that not all pregnancies are planned, and more and more people are becoming pregnant while receiving treatment with these drugs.

“Therefore, it was critical to generate evidence on the safety [of] these medications,” she added.

Risks of noninsulin treatments for pregestational diabetes

For this study, Dr. Hernández-Díaz and her team examined the data of more than 3.5 million pregnancies between 2009 and 2021. The data were taken from health databases in Finland, Iceland, Norway, Sweden, Israel, and the United States.

Of these pregnancies, almost 52,000 included people with pregestational type 2 diabetes. During the 3 months before or 3 months after becoming pregnant, about 15,000 of those individuals filled a prescription for a first- or second-line noninsulin antidiabetic medication.

During the study, researchers found that the infants of resulting from the pregnancies of people with pregestational type 2 diabetes had a substantially higher frequency of major congenital malformations — including cardiac malformations — than infants in the general population.

However, in infants born to people with type 2 diabetes who took a second-line noninsulin antidiabetic medication — including GLP-1 receptor agonists — the study did not find a greater major congenital malformation risk compared to infants exposed to insulin.

“The study shows that these new diabetes drugs do not pose a major risk of birth defects when used early in pregnancy, which is reassuring,” Dr. Hernández-Díaz said. “However, despite being the largest study in this field to date, covering more than 3.5 million pregnancies, relatively few women used these drugs, and some estimates were imprecise. Further studies are needed to confirm the results.”

Prenatal exposure to GLP-1 drugs to increase

The researchers also observed there was an increase in the use of second-line noninsulin antidiabetic medications throughout the study period, especially the use of GLP-1 receptor agonists in the U.S., suggesting the number of infants prenatally exposed to these drugs will continue to increase.

“During the study period, type 2 diabetes became more common among women of childbearing age and the proportion treated with newer antidiabetic medications, especially GLP-1 receptor agonists, increased in the U.S,” Dr. Hernández-Díaz said. “Since not all pregnancies are planned, more and more people were becoming pregnant while being treated with these drugs.”

“Nowadays, GLP-1 receptor agonists such as semaglutide — Wegovy, Ozempic — are also approved to treat obesity, suggesting the number of infants prenatally exposed to these drugs will continue to increase,” she continued.

“Therefore, an increasing number of patients and healthcare providers will be looking for information on the safety of GLP-1 receptor agonists when used early in pregnancy. Our findings are significant because they provide initial reassurance of safety for infants exposed to these medications during pregnancy.”

– Dr. Sonia Hernández-Díaz

Providing improvement for infant health

MNT also spoke with Dr. G. Thomas Ruiz, a board-certified OB/GYN and lead OB/GYN at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, about this study. Dr. Ruiz was not involved in this research.

Dr. Ruiz said he was not surprised that second-line noninsulin antidiabetic medications like GLP-1 receptor agonists are safe for use during pregnancy because they are very similar to medications used in the past to treat pregestational diabetes, such as metformin and glyburide.

“If you’re a type 2 diabetic and on one of those GLP-1 medications and it’s controlling your blood sugar, that’s actually what we want,” he explained. “We want your hemoglobin A1C ideally to be below seven before you get pregnant. Any medication that you can use to achieve that goal prior to pregnancy is going to help because patients with a hemoglobin A1C [of] more than 7, there’s a 15% anomaly rate, and most seriously have to do with the heart.”

“So if you look at [the] risks and benefits of a medication versus being in poor control when you get pregnant, you’re going to want to use those medications,” Dr. Ruiz continued. “Long term, we’ll get more information, but right now it looks like we have enough information that we’re not really seeing a significant effect on the fetus, only improvement because we have better glycemic control prior to pregnancy.”

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