OBJECTIVE: Primary endpoint is maternal and fetal complications during pregnancy, labor, and delivery after exposure to GLP-1 receptor agonists.
DATA SOURCES: A systematic search was conducted across PubMed, Embase, and Cochrane Central databases, including studies published from 2020 to 2025.
STUDY ELIGIBILITY CRITERIA: Included studies: (1) RCTs or cohorts; (2) exposure to GLP-1 RAs during pregnancy or preconception; (3) control group not exposed to GLP-1 RAs. Excluded studies: (1) without outcomes of interest; (2) lacking data transparency; (3) retracted; (4) abstracts, case reports, reviews; (5) no control group.
STUDY APPRAISAL AND SYNTHESIS METHODS: Six studies evaluated GLP-1 RA exposure during preconception or first trimester. Two authors screened studies; a third resolved disagreements. Risk of bias was assessed with ROBINS-I and RoB 2. Meta-analysis pooled continuous outcomes with mean differences and binary outcomes with odds ratios. Heterogeneity was evaluated via Cochrane Q and I². Subgroup analysis focused on first-trimester exposure.
RESULTS: No statistically significant differences in pregnancy outcomes between GLP-1 RA and control group, including fetal growth restriction or small for gestational age (p = 0.12), live births (p = 0.10), major birth defects (p = 0.79), miscarriages (p = 0.41), preterm delivery (p = 0.62); and stillbirths (p = 0.09). GLP-1 RAs were linked to a lower risk of congenital heart defects (p = 0.03), even in the subgroup analysis (p = 0.03), and showed no significant protective effect against gestational diabetes (p = 0.49). In subgroup analysis, there were no notable differences in miscarriage (p = 0.32), major birth defects (p = 0.83) and preterm delivery (p = 0.88); there were fewer live births that did not reach statistical significance (p = 0.06).
CONCLUSION: No statistically significant difference was observed between the control and intervention groups. GLP-1 RAs were connected to a lower risk of congenital heart defects.
