S4135 Ischemic Colitis Following Tirzepatide Therapy: An Emerging Clinical Observation

Introduction: Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus and obesity. While its efficacy in glycemic control and weight loss is well established, its safety profile continues to evolve. Gastrointestinal side effects such as nausea, vomiting, and diarrhea are common; however, serious adverse events involving the gastrointestinal tract, including ischemic colitis, have not been widely reported. Here we present a case of ischemic colitis temporally associated with the initiation of tirzepatide. Case Description: A 45-year-old woman with a history of anxiety, depression, and class II obesity presented to the emergency department with 2 days of nausea and painful hematochezia. She reported passing multiple blood clots but no stool. Her symptoms began 7 days after initiating a 5-day course of cephalexin for impetigo. She denied fevers, chills, or prior endoscopic evaluation. There were no recent changes to her medications which included fluoxetine, lithium, and lorazepam. Tirzepatide was initiated 8 months prior to presentation, with her last dose administered 5 days prior to presentation. The patient denied nonsteroidal anti-inflammatory drug use, alcohol, tobacco, or drug use. Laboratory results were notable for a C-reactive protein of 83.5 mg/L and white blood cell count of 11.6 × 10⁹/L. Computed tomography scan demonstrated nonspecific colitis involving the descending colon. Based on the clinical presentation and imaging, ischemic colitis was suspected. Tirzepatide was held and she was treated with 7 days of antibiotics. The patient reported complete resolution of symptoms at her 1 month follow up visit. A colonoscopy was performed 5 months after presentation and revealed normal descending colonic mucosa. Discussion: Ischemic colitis is typically associated with risk factors for mesenteric ischemia. However, emerging evidence suggests that GLP-1 receptor agonists may lead to ischemic colitis. In this case, symptoms began shortly after a 5-day course of cephalexin, which has been rarely associated with antibiotic-associated colitis. However, the timing of tirzepatide initiation and resolution of symptoms following its discontinuation raises suspicion for tirzepatide-associated ischemic colitis. While causality cannot be definitively established, this case supports the need for clinical awareness of rare complications associated with tirzepatide.