Human pregnancy outcomes after early glucagon-like peptide-1 receptor agonist exposure: A scoping review

Table 3 Pharmacovigilance and regulatory clinical-trial pregnancy data

Ref.	Evidence type	Data source	GLP-1RA exposure	Comparator	Exposure window/cessation timing	Maternal outcomes	Fetal/neonatal outcomes	Strength	Limitation	Interpretation
Zhou et al[24], 2025	Pharmacovigilance signal-detection study	FAERS 19-year data	354 pregnancy-related cases comprising 1671 ADR reports; liraglutide: 150; semaglutide: 106; dulaglutide: 52	FAERS comparator; sensitivity analysis using other pregnant women in FAERS	Any time during pregnancy	ROR025 signals-spontaneous abortion: 32.24, preeclampsia: 5.06, Imminent abortion: 1.40, stillbirth: 1.15	No MCM signal after sensitivity analysis using pregnant comparator	Broad real-world surveillance; multiple GLP-1RAs; used ROR and Bayesian IC; pregnancy-specific sensitivity analysis	No denominator; cannot estimate incidence or causality; reporting bias, duplicate reports, missing exposure timing, confounding by obesity/T2D/PCOS/HTN. No maternal baseline metabolic data available	Signal for spontaneous abortion and preeclampsia; hypothesis-generating, not risk-estimating
Parker et al[25], 2025	Regulatory clinical-trial inadvertent pregnancy dataset	FDA/EMA regulatory trial documents before approval	112 GLP-1RA-exposed pregnancies: Exenatide 4, lixisenatide 3, liraglutide 44, dulaglutide 7, albiglutide 6, semaglutide 41, tirzepatide 7	38 placebo/non-GLP-1RA comparator pregnancies	From pre-pregnancy reporting of incidental pregnancy and follow-up to delivery	1 preeclampsia; 1 oligohydramnios; 1 low birth weight; 1 mild gestational hypertension/cholestasis; 48 healthy live births; 24 spontaneous abortions; 3 ectopic pregnancies; 14 elective terminations; 13% elective termination in both exposed and unexposed	Healthy live birth: 43% vs 34%; MCM: 1.8% vs 5.3%; stillbirth: 0.9% vs 5.3%; spontaneous abortion: 22% vs 13%; ectopic pregnancy: 2.7% vs 7.9%; nonviable pregnancies: 25.2% exposed vs 26.3% unexposed; P = NR for any outcomes	Structured regulatory clinical trial pregnancy data; class-wide exposure across several GLP-1RAs; some comparator pregnancies available	Pregnancy was an exclusion criterion; post hoc extraction; small numbers; incomplete outcomes; no adjustment for maternal baseline risk; not a conventional cohort	Reassuring against a large teratogenic signal, but should be interpreted as intermediate evidence, not definitive safety evidence

Design-adapted appraisal of the pharmacovigilance and regulatory clinical-trial pregnancy evidence is provided in Supplementary Table 5. ADR: Adverse drug reaction; EMA: European Medicines Agency; FAERS: United States Food and Drug Administration Adverse Event Reporting System; FDA: Food and Drug Administration; GLP-1RA: Glucagon-like peptide-1 receptor agonist; HTN: Hypertension; MCM: Major congenital malformation; NR: Not reported/not retrievable; PCOS: Polycystic ovary syndrome; ROR: Reporting odds ratio; ROR025: Lower limit of the 95% confidence interval of reporting odds ratio; T2D: Type 2 diabetes.