Periconceptional GLP-1RA exposure safety varies on indication for use

Exposure to glucagon-like peptide 1 receptor agonists (GLP-1RAs) during pregnancy poses a modest increase in the risk of preterm birth in the context of diabetes treatment, but there is no evidence of increased obstetric complications when the drugs are exclusively used for weight management, according to new research.

Crude analysis of data from 756,643 pregnancies, including 529 where women were exposed to either liraglutide or semaglutide within 8 weeks of their last menstrual period, periconceptional exposure to GLP-1RAs was associated with a higher risk of obstetric complications such pre-eclampsia, gestational diabetes mellitus, and preterm birth compared with nonexposure. [ESHRE 2025, abstract deaf097.046]

When propensity score matching was applied to create a “pseudo-randomized” cohort, only preterm birth remained significantly associated with exposure to either liraglutide (adjusted odds ratio [aOR], 1.38, 95 percent confidence interval [CI] 1.01–1.89) or semaglutide (aOR, 1.62, 95 percent CI, 1.15–2.28) during pregnancy.

Further analysis revealed that the association between periconceptional GLP-1RA exposure and increased risk of preterm birth was present only when the drugs were used for diabetes treatment (liraglutide: aOR, 1.65, 95 percent CI, 1.13–2.40; semaglutide: aOR, 2.01, 95 percent CI, 1.37–2.94). There was no evidence of harm when the drugs were used exclusively for weight management (liraglutide: aOR, 1.06, 95 percent CI, 0.62–1.80; semaglutide: aOR, 0.81, 95 percent CI, 0.37–1.79).

“Most of the risk we saw before propensity score matching were from confounding,” noted principal investigator Dr David Westergaard from the Technical University of Denmark, Kongens Lyngby, Denmark.

Diabetes itself is a risk factor for preterm birth, and patients needing GLP-1RAs may have more severe diabetes, Westergaard said. “In Denmark, GLP-1RA is not the first-line treatment for people with pre-existing diabetes. It’s typically used for those that have more severe cases of diabetes.”

In clinical practice, women receiving GLP-1RA treatment should be advised to use contraception to prevent pregnancy, according to Westergaard. If exposure occurs, at least there will be some assurance that there is no increased risk of malformations or complications, he said. Nevertheless, individualized risk assessment should be performed and enhanced monitoring be provided to women with diabetes.

Westergaard emphasized that the reason women were prescribed GLP-1RAs is crucial for understanding the risks. He acknowledged the need for more data from larger populations to draw a definitive conclusion.