S4120 Delayed Onset Intolerance of GLP-1 Receptor Agonist Therapy: A Case Series of Adverse Reactions Requiring Hospitalization

Introduction: With the expanding clinical use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in managing diabetes, facilitating weight loss, and reducing cardiovascular risk, provider awareness of the medications' adverse effects remains incompletely characterized. While literature has numerous cases of major adverse events for GLP-1 RA use, no delayed onset adverse events have been reported. Here, we present 2 cases demonstrating delayed-onset intolerance resulting in adverse events and hospitalization. Case Description: A 63-year-old woman with a history of hypertension, coronary artery disease, hyperlipidemia, and type 2 diabetes mellitus presented with colicky abdominal pain radiating to the flank, associated with intractable nausea and vomiting. She reported medication adherence. On examination, she was afebrile but hypertensive (187/92 mmHg) with mild epigastric tenderness. Laboratory studies revealed hypokalemia (2.8 mEq/L) and hyperglycemia (177 mg/dL). Medication list revealed she had been on a GLP-1 RA for glycemic control for months with no recent dosage increase. The timing of symptom onset correlated with her weekly injection. Repeat esophagogastroduodenoscopy showed no significant pathology. She required hospitalization for intravenous fluids, electrolyte correction, and symptom control. Her symptoms resolved with cessation of the medication. A 49-year-old woman with hypertension, carotid artery stenosis, and history of stroke presented with acute onset of nausea, vomiting, diaphoresis, and central crushing chest pain shortly after restarting semaglutide 2 mg following a 2-week hold for colonoscopy. She denied abdominal pain, dyspnea, palpitations, or fever. Computed tomography angiography chest ruled out pulmonary embolism or aortic dissection with mild esophageal thickening, suggesting esophagitis. Given the clear temporal relationship with semaglutide reinitiation, her presentation was attributed to delayed onset GLP-1 RAs adverse event. Discussion: These cases highlight the need to recognize delayed-onset adverse reactions of GLP-1 RAs. Even patients who previously tolerated GLP-1 therapy well may develop severe gastrointestinal symptoms over time, possibly due to delayed gastric emptying or underlying gastroparesis. Careful monitoring is important, especially after restarting treatment following a medication holiday. As GLP-1 RAs continue to gain popularity, understanding their safety profile is essential for optimizing health care costs.