Key takeaways:
- The TriNetX dataset cannot determine whether predelivery GLP-1 RA prescriptions reflect inadvertent pregnancy exposure, planned washout periods, or continued first-trimester use — a key limitation for clinical interpretation.
- Prescriptions from cash-pay weight loss clinics and non-Epic-integrated systems are not captured, meaning the study likely underestimates total perinatal GLP-1 RA exposure.
- Investigators characterize the study as a high-level view of a now well-established phenomenon, with the next research priority being outcomes data on fetal and maternal effects in patients with documented periconceptional exposure.
The rapid rise in perinatal GLP-1 receptor agonist prescribing documented in a recent national EHR database study raises as many methodologic questions as clinical ones, according to a recent interview with study investigators.1
With the core prescribing trends covered in the first installment, Kevin Y. Xu, MD, MPH, and Jeannie C. Kelly, MD, MS, addressed the interpretive limitations that will shape how clinicians and researchers build on these findings.
A central question is whether the prescriptions captured in the predelivery window reflect inadvertent exposure during early pregnancy, planned discontinuation before conception, or continued use into the first trimester. The data cannot distinguish among those scenarios.
"From the data itself, we can't tell if these were inadvertent exposures, people purposely knowing that they're going to get pregnant coming off of these medications prior to pregnancy, or continuation of the medication through the first trimester," Kelly said.
Current guidelines across professional societies recommend discontinuing GLP-1 RAs 1 to 2 months before a planned conception and stopping immediately upon discovering an unplanned pregnancy. Kelly used that clinical context to inform her interpretation of the prescribing patterns.
“I don't think that there are that many physicians and clinicians out there prescribing GLP-1 medications purposefully throughout pregnancy," she said, suggesting the observed predelivery prescriptions likely reflect planned washout periods or inadvertent early-pregnancy exposure rather than intentional continuation.
Xu acknowledged the dataset's structural constraints. The TriNetX platform captures prescriptions integrated into the Epic EHR ecosystem, meaning prescriptions filled through cash-pay weight loss clinics or other non-integrated systems would not be reflected. The database also cannot confirm whether patients were actually taking the medication as prescribed, whether postpartum patients were breastfeeding, or at precisely what gestational age any given prescription was active.
