Continuing Glucagon-Like Peptide-1 Receptor Agonists Into the First Trimester of Pregnancy and Pregnancy Outcomes

BACKGROUND: Glucagon-like peptide-1 receptor agonist (GLP-1RA) use has increased among women of reproductive age, but limited data exist on safety in pregnancy. OBJECTIVE: To estimate the risk for nonlive birth, abnormal fetal growth, and major congenital malformation (MCM) with GLP-1RA dispensing in early pregnancy. DESIGN: In an observational cohort of pregnant women aged 16 to 55 years with a GLP-1RA dispensation in the 90 days before the last menstrual period (LMP), a target trial with 2 treatment strategies was emulated: continuation of dispensing into the first trimester (≥1 further dispensation), or noncontinuation. SETTING: Merative MarketScan U.S. insurance claims data (2011 to 2024). PARTICIPANTS: = 1467] among women with type 2 diabetes). MEASUREMENTS: Risk for nonlive birth was estimated using a weighted Kaplan-Meier estimator. Among live-birth pregnancies linked to infants, the weighted prevalence of MCM, small for gestational age (SGA), and large for gestational age (LGA) was estimated. RESULTS: The weighted risk for nonlive birth was 29.7% with continuation and 27.1% with noncontinuation (adjusted risk ratio, 1.09 [95% CI, 0.98 to 1.23]). Among 2529 live-birth pregnancies, 1443 (57.1%) received at least 1 GLP-1RA dispensation after LMP and 1499 (829 continuers) were linked to an infant. Weighted prevalence ratios for continuation versus noncontinuation were 1.29 (CI, 0.82 to 2.06) for SGA, 1.08 (CI, 0.84 to 1.40) for LGA, and 1.21 (CI, 0.83 to 1.82) for MCM. LIMITATION: Potential residual confounding by prior glycemic control. CONCLUSION: Risks for nonlive birth, SGA, LGA, and MCM were not definitively higher with continuation of GLP-1RAs into early pregnancy. However, estimates for MCM and SGA were imprecise and were compatible with both no increased risk and clinically relevant differences in risk. PRIMARY FUNDING SOURCE: National Institutes of Health.