Abstract
Tirzepatide has been approved for the management of obesity, obstructive sleep apnea, and type 2 diabetes mellitus; while gastrointestinal side effects are commonly seen, ischemic colitis has been only rarely described. We present the case of a 32-year-old woman with no prior medical history who developed hematochezia and abdominal pain after six weeks of tirzepatide therapy for weight loss. Laboratory evaluation showed neutrophilic leukocytosis without anemia or electrolyte abnormalities, and stool studies were negative for infection. A CT of the abdomen and pelvis excluded obstruction or wall thickening but incidentally revealed hepatic steatosis and adnexal lesions. Colonoscopy demonstrated patchy erosions, erythema, and ulcerations in the sigmoid and descending colon, with biopsy confirming ischemic colitis. She was managed conservatively with bowel rest, intravenous fluids, and close monitoring, with stable hemoglobin and complete resolution of symptoms. Although ischemic colitis is more typically linked to vascular disease, hypotension, or vasoconstrictive drugs, recent reports have suggested an association with glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide and tirzepatide. The temporal relationship with tirzepatide initiation, absence of infection, and confirmatory histology strongly support drug-induced ischemia in this case, underscoring the importance of clinician awareness of this rare but significant complication in patients presenting with rectal bleeding or abdominal pain while on incretin-based therapy.