Pregnancy Outcomes After Semaglutide Exposure: A Summary of the Study by Kolding et al. (2025)

The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as semaglutide for the treatment of type 2 diabetes mellitus and obesity has raised concerns regarding their safety during pregnancy. Because semaglutide is generally not recommended for pregnant women, data on inadvertent exposure during early pregnancy remain limited. In their 2025 study, Pregnancy Outcomes After Semaglutide Exposure, Kolding and colleagues investigated pregnancy outcomes among women exposed to semaglutide during pregnancy, providing important evidence for clinicians and patients.

The study aimed to evaluate whether semaglutide exposure during pregnancy was associated with an increased risk of adverse fetal or maternal outcomes. Using data from national health registries, the researchers identified pregnancies with documented semaglutide exposure and compared outcomes with those of unexposed pregnancies and relevant comparison groups. Outcomes of interest included major congenital malformations, pregnancy loss, preterm birth, low birth weight, and other neonatal complications.

The authors found that semaglutide exposure during pregnancy was relatively uncommon, reflecting current recommendations to discontinue the drug before conception. Overall, the study did not demonstrate a substantial increase in the risk of major congenital malformations among pregnancies exposed to semaglutide. The rates of birth defects observed in exposed pregnancies were broadly comparable to those seen in the reference populations. However, the investigators emphasized that the number of exposed pregnancies was limited, reducing the statistical power to detect small increases in risk.

The study also evaluated secondary pregnancy outcomes. While some differences in pregnancy and neonatal outcomes were observed, these findings were difficult to interpret because women receiving semaglutide often had underlying conditions such as obesity, diabetes, or metabolic disorders, which themselves are associated with adverse pregnancy outcomes. Consequently, distinguishing the effects of the medication from the effects of maternal disease remains challenging.

A major strength of the study was its use of large population-based registry data, which enabled the identification of real-world pregnancies exposed to semaglutide. Nevertheless, the authors acknowledged several limitations, including the relatively small number of exposed pregnancies, potential confounding factors, and limited information regarding dosage, timing of exposure, and lifestyle variables.

The findings contribute to the growing body of evidence regarding the reproductive safety of GLP-1 receptor agonists. Although the results provide some reassurance that inadvertent early-pregnancy exposure to semaglutide may not be associated with a markedly increased risk of major congenital malformations, the evidence remains insufficient to establish safety conclusively. Therefore, current recommendations to avoid semaglutide during pregnancy and discontinue treatment before planned conception remain appropriate.

In conclusion, Kolding et al. (2025) provide valuable observational data suggesting that semaglutide exposure during pregnancy is not associated with a large increase in major birth defects. However, because of limited sample size and residual uncertainty, caution is still warranted. Further studies involving larger numbers of exposed pregnancies are needed to clarify the safety profile of semaglutide during pregnancy and to guide evidence-based clinical recommendations.

Reference

Kolding L, Henriksen JN, Sædder EA, Ovesen PG, Pedersen LH. Pregnancy Outcomes After Semaglutide Exposure. Basic Clin Pharmacol Toxicol. 2025;136(4):e70021. doi:10.1111/bcpt.70021. PMID: 40083043. PMCID: PMC11906903.