S3719 Tirzepatide-Induced Eosinophilic Colitis: A Rare Gastrointestinal Presentation of a GLP-1 Receptor Agonist

Introduction: Tirzepatide, a dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, has become widely used for managing type 2 diabetes and weight loss. While gastrointestinal (GI) side effects are well established, immune-mediated side effects are not well characterized. We report a novel case of eosinophilic colitis secondary to Tirzepatide use. Case Description/Methods: A 56-year-old man with a history of type 2 diabetes mellitus, hypertension, and gastroesophageal reflux disease (GERD) presented with 1 week of vomiting, diarrhea, and left lower quadrant abdominal pain. His symptoms began shortly after increasing his dose of tirzepatide. At presentation, the patient’s clinical findings were heart rate 98 bpm, White blood cell count 17.72 K/μL, Absolute eosinophils 1.14 K/μL, Sodium 132 mmol/L, Creatinine 2.1 mg/dL and Lactate 2.9 mmol/L. Abdominal imaging showed enteritis prompting empiric antibiotics, later discontinued after a negative GI pathogen panel. Given the patient’s persistent diarrhea and dehydration, the decision was made to perform bidirectional endoscopy as an inpatient. Bidirectional endoscopy was unremarkable. Given his diarrhea duodenal biopsies and random colonic biopsies were obtained. Colonic biopsy showed increased eosinophils and lymphoplasmacytic infiltrates. Following de-escalation of tirzepatide, his symptoms gradually resolved. Repeat colonoscopy 2 months later showed no residual eosinophilic inflammation. Discussion: To our knowledge, this is the first documented case of eosinophilic colitis associated with tirzepatide. Although GLP-1 receptor agonists have been implicated in eosinophilic fasciitis and other immune phenomena, the role of GLP-1 and GIP receptor modulation in eosinophil biology remains incompletely understood. Emerging studies suggest that GLP-1 analogs influence eosinophil activation and cytokine secretion, although effects may vary by disease state and individual susceptibility. As tirzepatide use expands particularly for weight loss, clinicians should maintain heightened awareness of potential immune-mediated complications. Prompt recognition and drug withdrawal are critical to improving patient outcomes. Further investigation is warranted to clarify the immunologic mechanisms underlying eosinophilic gastrointestinal toxicity associated with GLP-1/GIP receptor agonists.