CureusDuodenal Ulcer Perforation Following Tirzepatide Injections for Weight Loss Management: A Case Report

⚠️ Rare but High Risk Safety Event

Authors reported a 43-year-old woman who developed a perforated duodenal ulcer approximately two weeks after increasing tirzepatide from 2.5 mg to 5 mg weekly for obesity management. CT imaging demonstrated a localized retroperitoneal perforation involving the third portion of the duodenum. The patient was treated conservatively with bowel rest, proton pump inhibitor therapy, antibiotics, and supportive care, ultimately recovering without surgery. The report represents only the second published case described by the authors linking tirzepatide to duodenal ulcer perforation. However, a major study limitation is the absence of H. pylori testing, preventing exclusion of a well-established alternative cause.

Clinical Considerations

• The patient developed severe epigastric and right upper quadrant pain approximately two weeks after tirzepatide dose escalation.
• CT imaging confirmed a localized retroperitoneal perforated duodenal ulcer involving the third portion of the duodenum.
• Conservative management resulted in recovery without operative intervention, and follow-up endoscopy showed no residual duodenal pathology.
• The patient reportedly lacked documented NSAID exposure and other common ulcer risk factors, though risk-factor assessment was incomplete.
• H. pylori status was never determined, representing a critical limitation because infection is a well-established cause of peptic ulcer disease and perforation.
• A single case report can identify a potential safety signal but cannot establish causality or estimate risk.

Practice Applications

• Recognize severe or persistent abdominal pain in patients receiving tirzepatide as requiring prompt clinical evaluation.
• Interpret this case as hypothesis-generating rather than evidence of a confirmed drug-related complication.
• Review alternative causes of peptic ulcer disease, including H. pylori infection, NSAID exposure, smoking, and corticosteroid use.
• Monitor emerging pharmacovigilance reports and larger observational studies evaluating serious upper gastrointestinal adverse events.
• Avoid assuming that temporal association alone establishes tirzepatide as the cause of ulcer perforation.