Clinical Outcomes of Glucagon-Like Peptide-1 Receptor Agonist (GLP-1 RA) and Glucagon-Like Peptide-1/Glucose-Dependent Insulinotropic Polypeptide Receptor Agonist (GLP-1/GIP RA) Exposures Presenting to the Emergency Department.

Abstract

Background: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) and glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor agonist (GLP-1/GIP RA) use has become increasingly popular, leading to a rise in exposure calls to poison centers.

Objective: To characterize the clinical effects and outcomes following GLP-1 and GLP-1/GIP RA exposures managed in the emergency department and identify factors prevalent among asymptomatic and symptomatic patients.

Methods: This was a retrospective cohort study of patients exposed to a GLP-1 or GLP-1/GIP RA across 3 poison centers between 2005 and 2023. Patients were included if they were managed at a healthcare facility and excluded if they coingested a medication that may cause significant hypoglycemia, the exposure was for suicidal intent, or the exposure was not followed to a known clinical outcome.

Results: ToxSentryWeb identified 186 potential cases; 152 met the study criteria (130 symptomatic and 22 asymptomatic patients). Nausea (92%) and vomiting (76%) were the most reported clinical effects in the symptomatic group. Hypoglycemia occurred in 9% of patients. Most of the clinical effects lasted 8 to 24 hours. These effects were managed primarily with intravenous fluids (56%) and/or antiemetics (51%). Notably, a higher proportion of patients in the asymptomatic group were exposed to dulaglutide, and a higher proportion of patients in the symptomatic group were exposed to semaglutide.

Conclusion and relevance: This study reveals a critical gap in understanding the clinical outcomes of GLP-1 and GLP-1/GIP RA exposures. Most patients experience mild gastrointestinal symptoms, which typically resolve within 8 to 24 hours with short-term observation. However, hypoglycemia was observed at a higher rate than previously reported despite the absence of concomitant hypoglycemic agents, underscoring the need for close monitoring. These findings suggest that providers should tailor observation times based on symptom severity, while emphasizing patient education on proper administration to prevent misuse and ensure optimal therapeutic outcomes.