Abstract Background In 2005, the United States (U.S.) Food and Drug Administration (FDA) approved the first Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA) as adjunctive therapy to improve glycemic control in type 2 diabetes. In 2021, the FDA approved semaglutide for chronic weight management. We aim to characterize GLP-1RAs related calls to all U.S poison centers (PCs). Methods We conducted a retrospective review of the U.S. National Poison Data System (NPDS) between 2005 and 2023 for all GLP-1RA exposures. All 55 PCs covering the entire U.S. population submit, in near real-time, de-identified case data to NPDS after providing poison exposure management to callers from the general public and health care providers. Results During the study period, U.S. PCs handled 13,692 GLP-1RAs related calls, of which 12,451 were a GLP-1RA single substance exposures. In 2023, PCs received 4,414 GLP-1RA related calls, compared to 234 in 2014 (a twenty-fold increase over 10 years). Seventy three percent of exposures involved females (n = 10,017). The main reasons for exposure were therapeutic errors (n = 10,213; 75%), adverse drug reactions (n = 1,222; 9%) and suspected suicide (n = 557; 4%). Gastrointestinal symptoms, such as nausea (n = 2,913; 23%), vomiting (n = 2,515; 20%), and abdominal pain (n = 593; 5%), and neurological symptoms, including central nervous system depression (n = 191; 1.5%), dizziness (n = 563; 5%) and headache (n = 495; 4%) were the most commonly reported clinical effects in single substance exposures. Hypoglycemia was reported in 431 cases (3.5%), Most single substance exposures were managed outside a healthcare facility (n = 8.573; 69%), and hospital admission was reported in 5% of exposures (n = 601). Conclusions PCs are well positioned to monitor trends in GLP-1RAs human exposures and associated adverse events and therapeutic errors. Based on available data, PCs can manage specific cases-types without referral to the hospital, preventing unnecessary healthcare utilization. Key messages • Poison centers are well positioned to monitor trends in GLP-1RAs adverse events. • Poison centers can prevent unnecessary healthcare utilization.