The introduction of tirzepatide marks a significant advancement in the management of type 2 diabetes mellitus (T2DM) and obesity. This dual synthetic polypeptide, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 receptor agonist (GLP-1 RA) acts through incretin pathways and stimulates insulin sensitivity while slowing gastric emptying. While these benefits are well established, the drug's effects on gastrointestinal motility may predispose susceptible patients to several gastrointestinal complications. We present a rare case of severe small bowel obstruction in a 61-year-old woman with diabetes and morbid obesity who had been on long-term tirzepatide (Mounjaro) therapy. She presented to our hospital with acute, severe, diffuse abdominal pain, accompanied by dry heaving. She denied any hematemesis, melena, or hematochezia. She was receiving tirzepatide 2.5 mg weekly, then titrated to 5 mg after one month, and this dose was maintained for over a year. Since initiation, her hemoglobin A1c decreased from 8.6% to 5.6%, insulin therapy was discontinued, and she achieved significant weight loss, with improved liver function and laboratory parameters. However, she developed progressive constipation, with only one to two bowel movements per week, representing a marked change from her baseline. CT scans of the patient's abdomen and pelvis revealed multiple dilated, fluid-filled small bowel loops, with a transition point in the midline lower pelvis. There was also moderate gastric distention and moderate free fluid in the pelvis. No evidence of perforation or mass was seen. The patient was initially managed with nasogastric decompression, bowel rest, intravenous fluids, and analgesia. As her symptoms persisted and repeated examinations raised concern for peritonitis, she underwent laparoscopic adhesiolysis, which was converted to exploratory laparotomy due to dense adhesions. Intraoperatively, a closed-loop obstruction was identified, caused by adhesive disease and an internal hernia, with 25 cm of necrotic small bowel requiring resection. Pathologic evaluation of the resected specimen revealed edema, congestion, and ischemic changes. Although adhesive disease was the direct cause of the obstruction, the temporal relationship between tirzepatide (Mounjaro) initiation, progressive constipation, and eventual obstruction suggests a contributory role. Our case suggests tirzepatide-induced motility changes may worsen baseline constipation and precipitate obstructive complications in predisposed patients. Clinicians should monitor bowel function closely in high-risk patients and have a low threshold for imaging in the presence of obstructive symptoms.
