Study links GLP-1 use to some pregnancy risks — but the research has key caveats

Ozempic and similar drugs are not recommended for use in pregnancy, but stopping the medications before conception may also come with some risks, new data suggest.

These data should be interpreted as an early signal that warrants further investigation, a researcher involved in the study told Live Science.

The analysis had key limitations. The women who did and did not use the weight-management drugs may not have been completely comparable, and the study was not designed to capture potential benefits of taking Ozempic or a similar drug before pregnancy.

"We don't know if there's a benefit, or if there's increased risk, if you get to pregnancy at a lower weight and then come off the medication," said study first author Dr. Jacqueline Maya, a pediatric endocrinologist and physician-investigator at Massachusetts General Hospital who studies how events in pregnancy impact the health of both mother and child.

For now, Maya said the new study's results are a "heads up" for doctors. "We just need to monitor [these patients] closely, because there were some obstetric outcomes that we need to keep an eye on," she told Live Science.

An understudied population

Drugs like Ozempic, Wegovy and Zepbound are "glucagon-like peptide-1 receptor agonists," or GLP-1s, for short. GLP-1s regulate weight and improve blood sugar through several mechanisms, such as by slowing down digestion and altering how the brain sends "hunger signals." The drugs have been tied to dozens of knock-on benefits, including a lower risk of both heart attack and dangerous blood clots.

But studies in mice and rabbits suggest that the drugs may raise the risk of birth defects and pregnancy loss and restrict fetal growth. "So, the recommendation currently is to stop the medication prior to conception," Maya said.

This recommendation means that there's a population of women who stop using GLP-1s before pregnancy, raising questions about whether that can cause any negative effects. In the general population prescribed GLP-1s, stopping the medications comes with a rebound in weight gain and related metrics, such as blood pressure, cholesterol and blood sugar. But these effects haven't been studied much in pregnancy.

"To date, only 1 other study has examined gestational weight gain after GLP-1RA use," and "only a handful" have looked at links between the drugs and other adverse pregnancy outcomes, epidemiologists Carolyn Cesta, Jennifer Hutcheon and Kari Johansson wrote in a commentary of the new research.

To help fill this gap, the researchers looked back at hundreds of singleton pregnancies delivered in the Mass General Brigham health system between 2016 and 2025. They focused on about 450 pregnancies in which mothers used GLP-1s between three years before and 90 days after conception. About 50% stopped taking the medications within six months of conception, about 34% stopped earlier than that, and 17% stopped after conception.

Just prior to pregnancy, the average BMI of these mothers was about 36, which is categorized as obese. The researchers compared these GLP-treated individuals against mothers who had never used the medications but also had BMIs of about 36 before pregnancy. The full range of BMIs in both groups ran from "healthy" to "severely obese," with similar proportions of people in each category in each group.

Those who had taken and then stopped GLP-1s had an increased risk of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy, such as gestational high blood pressure and preeclampsia, the analysis found. Additionally, the GLP-1-treated group gained more weight during pregnancy — about 30 pounds (13.7 kilograms), on average, compared with an average of 23 pounds (10.5 kg) for the comparison group.

And notably, more people in the GLP-1-treated group had "excessive gestational weight gain," which is associated with health risks for both the mother and the baby. The amount of weight gain that's considered "excessive" varies depending on the individual's pre-pregnancy BMI, according to guidelines from the National Academy of Medicine. About 65% of the GLP-treated group had "excessive" weight gain, compared with 49% of the comparison group.

Within the treated group, the timing of the GLP-1 stoppage didn't seem to have a huge effect on the results. "We expected, I think, a more pronounced change, but our results were pretty similar," Maya said. It may be that excess weight gain drove the other pregnancy outcomes observed, but the current data can't demonstrate that for certain, she noted.

Questions remain

One significant limitation of the study was that the team compared people who had taken GLP-1s with people of similar body mass who had never been on the drugs. In other words, the researchers looked at the treated group only after they were exposed to GLP-1s, when their BMIs had likely fallen lower than their pre-prescription weights, the commentary writers noted.

In the future, the researchers also want to take people's pre-GLP weights into account and find a comparison group with comparable baseline BMIs, Maya said. These data, which they're working to gather now, would help contextualize whether there are any benefits of using the drugs to lose weight prior to conception, even if you then have to come off the drugs during pregnancy.

The commentary authors added that some of the new study's results appear to contradict other research. For instance, some studies have linked GLP-1 use to a lower risk of hypertensive disorders of pregnancy. But that may be because those previous studies included a higher proportion of people who were prescribed GLP-1s for diabetes, while the new study skewed toward people who specifically took the medicines for obesity.

Like the new study, this previous work compared GLP-1 users with "women with similar BMI near the start of pregnancy but with no history of GLP-1RA use," the commentary authors added. This might be common across studies due to databases having a "paucity of data" on patients' pre-treatment BMIs, and the fact that it's challenging to then link that BMI data to prescription and pregnancy records.

But these data gaps further underscore the need to study this population, as currently, there is "limited or no clinical guidance" on the use of GLP-1s prior to conception, the commentary authors wrote. The new research, published Monday (Nov. 24) in JAMA, begins to close the gap, but more studies are needed to understand the medications' pros and cons for people planning to conceive.

"It is critical that we strive to generate the evidence needed both to inform obstetric care and guide treatment initiation decisions," the commentary authors concluded.

As is common in drug research, initial trials of GLP-1s excluded people who said they were planning to conceive, but that population still uses these medications. "That's how this research unfolds," Maya said, "and then slowly, we come in and advocate for some of these vulnerable groups that weren't included in the initial studies."