Abstract
INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are therapies for type 2 diabetes whose use expanded sharply after semaglutide's 2021 approval for obesity. Although gastrointestinal effects are well described, national patterns of acute GLP-1 RA exposures are poorly characterized. This study evaluated trends in GLP-1 RA exposures reported to U.S. poison centers, focusing on demographic shifts, exposure circumstances, and clinical outcomes before and after the 2021 FDA approval. METHODS: We analyzed human GLP-1 RA exposures reported to the National Poison Data System from 2012 to 2023, using July 1, 2021, to define pre- and post-approval periods. Demographics, exposure characteristics, therapies, and medical outcomes were compared using standardized statistical tests. Quarterly call counts were modeled with segmented Poisson regression to assess changes in reporting trajectory. RESULTS: A total of 10,033 exposures were identified (3,113 pre-approval; 6,920 post-approval). Semaglutide predominated post-approval (64.2%). The exposed population shifted younger and more female. Most cases were unintentional therapeutic errors with mild gastrointestinal symptoms. The proportion managed in or referred to a health care facility increased from 23.0% to 33.5% (RR = 1.46, [95% CI: 1.36, 1.57], p < 0.001). Segmented Poisson modeling demonstrated a significant inflection in call volume, with semaglutide exposures increasing an additional 9.9% per quarter after approval. CONCLUSIONS: GLP-1 RA exposures rose sharply following semaglutide's weight-loss approval, accompanied by increased health care utilization despite generally mild clinical effects. Although multiple factors likely contributed to these trends, improved patient counseling and clearer poison center guidance may help reduce preventable therapeutic errors and unnecessary emergency evaluation.