In a recent study published in the journal Scientific Reports, researchers evaluated the impact of maternal exposure to glucagon-like peptide-1 (GLP-1) receptor agonists during pregnancy on congenital malformations and other adverse outcomes. The findings offer a cautious reassurance, but the study highlights the need for further research to establish the safety of these drugs during pregnancy.
The Rising Use of GLP-1 Receptor Agonists
The study comes at a time when the use of weight-loss and diabetes medications, including GLP-1 receptor agonists, is on the rise globally. This has led to more women of reproductive age becoming pregnant while receiving these treatments, often without realizing they are pregnant. The potential for unintended pregnancies is higher due to the drugs' ability to restore ovulatory function in women with obesity-related reproductive dysfunction.
However, the limited human safety evidence surrounding these medications poses a challenge for healthcare professionals providing advice to patients. The study aims to address this knowledge gap by examining the association between GLP-1 receptor agonists and pregnancy outcomes.
Study Methodology
The researchers conducted a systematic review and meta-analysis, following the PRISMA 2020 guidelines and registering the protocol in PROSPERO. They searched multiple databases, including PubMed, MEDLINE, Embase, Web of Science, and Reprotox, up to January 2026. The search included cohort and case-control studies assessing maternal exposure to GLP-1 receptor agonists from 90 days before conception to the end of pregnancy, with an unexposed comparator group.
The study excluded reviews, editorials, animal studies, and pharmacovigilance reports. Risk of bias was assessed using the ROBINS-I tool, and methodological quality was evaluated with the Newcastle-Ottawa Scale. The GRADE system was applied to assess the certainty of evidence for each outcome.
Key Findings
The analysis included seven cohort studies with over 40,000 pregnancies exposed to GLP-1 receptor agonists. The timing of exposure varied, with some studies focusing on the first trimester. The most frequently reported drugs were semaglutide and liraglutide, followed by exenatide and dulaglutide.
The study found no statistically significant increase in the overall risk of congenital disabilities associated with GLP-1 receptor agonist exposure during pregnancy (OR 1.11, 95% CI 0.82-1.51). Similarly, first-trimester exposure showed no significant increase in major congenital malformations (OR 1.39, 95% CI 0.73-2.65).
However, the analysis identified a statistically significant association with urinary congenital malformations (OR 1.24, 95% CI 1.05-1.47), driven by one large cohort. This finding is considered limited due to the lack of specific urinary malformation subtypes and potential confounding by maternal diabetes or obesity.
None of the other adverse pregnancy outcomes, including stillbirth, spontaneous abortion, small-for-gestational-age births, and preterm birth, reached statistical significance. However, the study noted substantial heterogeneity and imprecise estimates, emphasizing the need for further research.
Conclusion and Future Directions
The authors concluded that maternal exposure to GLP-1 receptor agonists did not significantly associate with major congenital malformations, stillbirth, spontaneous abortion, small for gestational age, or preterm birth. While the study provides cautious reassurance, it highlights the low certainty of evidence and the need for larger population studies with standardized exposure definitions and comprehensive confounding adjustments.
The findings suggest that while GLP-1 receptor agonists may not pose a significant risk for most pregnancy outcomes, further research is essential to establish their safety for routine use throughout pregnancy. The study's limitations, including varying comparator groups and exposure definitions, underscore the importance of continued investigation in this area.
