Case Presentation: A 39-year-old male with obesity on tirzepatide presented with sudden-onset severe abdominal pain and multiple episodes of hematochezia. In the emergency department, he was afebrile with normal heart rate and oxygenation, and blood pressure of 165/78 mmHg. Labs revealed mild leukocytosis of 11.4 K/µL, CRP 20.2 mg/L, normal hemoglobin, lactate, and metabolic panel. CT abdomen/pelvis demonstrated circumferential wall thickening from the splenic flexure to the distal descending colon, concerning for ischemic colitis. CT angiography confirmed patent mesenteric vessels without evidence of occlusion. He was admitted for intravenous fluids and started on empiric piperacillin–tazobactam.Colonoscopy revealed linear ulcerations and friable mucosa in the descending colon, and biopsy confirmed ischemic colitis. Infectious stool testing, including C. difficile PCR, stool culture, and ova/parasites, was negative. Stool calprotectin was markedly elevated at 2320 µg/g. With no autoimmune history and low suspicion for inflammatory bowel disease or vasculitis, autoimmune evaluation was deferred.By hospital day two, both abdominal pain and hematochezia had improved. His diet was gradually advanced, and he was discharged home tolerating oral intake. His ischemic colitis was ultimately attributed to GLP-1 receptor agonist therapy, and tirzepatide was discontinued indefinitely.
Discussion: Ischemic colitis results from transient or sustained hypoperfusion of the colon, most often in watershed regions. Although typically seen in older adults with atherosclerosis, younger patients may develop it due to medication-induced hypovolemia or altered mesenteric perfusion. Prior reports describe associations between ischemic colitis and agents causing dehydration, such as diuretics. GLP-1 receptor agonists—such as tirzepatide and semaglutide— have emerged as potential contributors to colonic hypoperfusion in otherwise healthy individuals through delayed gastric emptying, constipation, increased satiety, and reduced oral intake [1],[2]. The patient’s clinical presentation, imaging, and colonoscopic findings were consistent with nonocclusive ischemic colitis likely secondary to GLP-1–induced dehydration and constipation. His rapid clinical improvement with conservative management and discontinuation of the medication highlights the importance of early identification and supportive care in mild to moderate ischemic colitis. This vignette exemplifies an increasingly relevant case in hospital medicine– acute presentations requiring prompt recognition to prevent unnecessary invasive interventions.
Conclusions: GLP-1 receptor agonists, while highly effective for weight loss and glycemic control, are associated with a spectrum of gastrointestinal adverse effects ranging from nausea, vomiting, diarrhea, and constipation to more severe reactions like gastroparesis, cholecystitis, pancreatitis, and, in rare cases, ischemic colitis [3].As use of these agents continue to rise, hospitalists must balance their substantial metabolic benefits with the potential for serious complications and need to remain vigilant for atypical presentations. Proactive counseling on maintaining adequate hydration and need for prophylactic bowel regimens when appropriate may mitigate risk. Close outpatient follow-up is essential to identify early warning signs, prevent progression to severe complications, and reduce hospitalizations related to medication side effects.