S3696 Ischemic Colitis in the Setting of Tirzepatide-Induced Constipation: A Potential Adverse Effect

Introduction: Glucagon-like peptide-1 receptor agonists, including tirzepatide, are widely used for diabetes and weight loss. While gastrointestinal side effects such as constipation and delayed gastric emptying are well-documented, ischemic colitis (IC) has been infrequently reported. Traditional risk factors for IC include advanced age, atherosclerosis, hypertension, diabetes, hypoperfusion states, and medications that reduce mesenteric blood flow or promote thrombosis. This case highlights tirzepatide as a potential risk factor for IC. Case Description/Methods: A 51-year-old woman with prediabetes on tirzepatide, hypertension, and prior abdominoplasty was admitted with severe abdominal pain and constipation. Two days prior, she underwent rotator cuff repair; tirzepatide had been held for a week preoperatively and resumed the day after surgery. She was taking intermittent oxycodone for postoperative pain. Due to worsening abdominal pain and lactic acidosis, she underwent emergent surgery within 12 hours of presentation. Intraoperative colonoscopy revealed severe ischemic colitis from the splenic flexure to the proximal transverse colon, requiring subtotal colectomy with end ileostomy. Pathology confirmed acute inflammation. Infectious stool studies were negative, and postoperative computed tomography (CT) angiography showed patent mesenteric vessels. Tirzepatide was discontinued. Discussion: Tirzepatide’s pharmacologic effects of delayed gastric emptying and decreased intestinal motility via the ileal brake may predispose to colonic hypoperfusion, particularly in watershed areas. Chronic diabetes-related microangiopathy may further increase ischemic risk. In this case, the patient's limited risk factors, the timing of tirzepatide resumption alongside opioid use, likely contributed to severe constipation causing IC post-operatively. While a definitive association remains unclear, this case adds to the few reported instances of IC in patients on tirzepatide. Further studies are needed to clarify this potential relationship.