GLP-1 Receptor Agonist Exposure During Pregnancy Not Linked to Major Malformations in Meta-Analysis
Background
The increasing use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GLP-1/GIP receptor agonists among reproductive-aged women for conditions like obesity, type 2 diabetes, and polycystic ovary syndrome (PCOS) necessitates a clear understanding of their reproductive safety. Despite their efficacy in cardiometabolic disease management, robust data on fetal outcomes following periconceptional or gestational exposure have been limited. This gap creates uncertainty for clinicians and patients, as current standard-of-care often advises discontinuation of these agents prior to or during pregnancy due to theoretical risks and lack of comprehensive human safety data.
Study Design
Researchers conducted a systematic review and meta-analysis, searching PubMed, MEDLINE, Embase, Web of Science, and Reprotox databases from inception through January 2026. The objective was to assess the risk of any and major congenital malformations, as well as other adverse pregnancy outcomes. The analysis included seven cohort studies encompassing over 40,000 exposed pregnancies. Primary endpoints focused on the risk of congenital malformations, while secondary endpoints included stillbirth, spontaneous abortion, small for gestational age (SGA), and preterm birth, comparing outcomes in pregnancies exposed to GLP-1 receptor agonists versus unexposed controls.
Results
Maternal exposure to glucagon-like peptide-1 receptor agonists at any point during pregnancy was not associated with a statistically significant increase in any congenital malformations (OR, 1.11; 95% CI 0.82-1.51). Specifically, first-trimester exposure did not significantly increase the risk of major congenital malformations (OR, 1.39; 95% CI 0.73-2.65). Furthermore, the meta-analysis observed no significant risk increase for other critical adverse outcomes, including stillbirth, spontaneous abortion, small for gestational age, or preterm birth. This provides reassuring evidence across several key safety parameters. However, a significant association for urinary malformations was noted (OR, 1.24; 95% CI 1.05-1.47).
Key Findings
- Maternal GLP-1 RA exposure during pregnancy was not associated with a significant increase in any congenital malformations (OR, 1.11; 95% CI 0.82-1.51).
- First-trimester GLP-1 RA exposure did not significantly increase the risk of major congenital malformations (OR, 1.39; 95% CI 0.73-2.65).
- No significant risk increase was observed for stillbirth, spontaneous abortion, small for gestational age, or preterm birth.
- A significant association for urinary malformations was noted (OR, 1.24; 95% CI 1.05-1.47), but based solely on unadjusted data.
Why It Matters
This meta-analysis offers cautiously reassuring evidence regarding the reproductive safety of GLP-1 RAs, particularly for women who may experience unplanned pregnancies while on these medications. While current guidelines often recommend discontinuing GLP-1 RAs before conception, these findings suggest that accidental exposure during early pregnancy may not carry a significantly elevated risk of major congenital malformations. This information is crucial for patient counseling, helping to alleviate anxiety and inform shared decision-making. However, the low certainty of evidence and the unadjusted signal for urinary malformations highlight the ongoing need for more robust, prospectively collected data to definitively guide clinical practice and potentially revise existing protocols for reproductive-aged women.
glp-1-ra
pregnancy
congenital-malformations
meta-analysis
reproductive-safety
diabetes