Boerhaave syndrome after semaglutide use

A case report published in the Journal of Cardiothoracic Surgery on 12 June 2026 describes what the authors call the first documented instance of Boerhaave's syndrome, a full-thickness spontaneous esophageal perforation, associated with semaglutide use^[1]. The patient, a woman in her 50s, had restarted semaglutide at the maximum 2.4 mg weekly dose without following the standard dose-escalation schedule. She developed forceful vomiting, then acute chest pain, and was ultimately diagnosed with esophageal rupture.

What is Boerhaave's syndrome

Boerhaave's syndrome is a spontaneous rupture of the oesophagus, typically caused by a sudden rise in intra-oesophageal pressure during forceful vomiting. Unlike a Mallory-Weiss tear, which involves only the mucosal layer, Boerhaave's is a full-thickness perforation through all layers of the oesophageal wall. It leads to contamination of the mediastinum with gastric contents, triggering a chemical injury followed by polymicrobial infection. A 2025 narrative review in Diagnostics described the resulting cascade as progressing from perforation to septic mediastinitis, endothelial dysfunction, and ultimately multi-organ failure if not interrupted^[2].

The classic presentation, sometimes called Mackler's triad, involves vomiting followed by chest pain and subcutaneous emphysema (air under the skin). Mortality remains high when diagnosis or treatment is delayed, partly because the initial symptoms can mimic a heart attack, a pulmonary embolism, or a perforated ulcer. The condition is rare in the general population, and most emergency physicians see it infrequently, which contributes to delayed recognition.

What happened in this case

The patient had previously tolerated semaglutide at a lower dose. She then restarted the drug at the maximum 2.4 mg weekly dose without gradual titration. Within a day she developed severe nausea and vomiting, followed by acute chest pain that progressed to vasopressor-dependent shock and respiratory failure requiring intubation^[1].

Imaging revealed pneumomediastinum (air in the chest cavity around the oesophagus) and bilateral pleural effusions. An oesophagram confirmed a contained oesophageal perforation. She was initially treated with endoscopic stent placement, nasojejunal feeding, and chest-tube drainage, and improved.

Two months later she returned with necrotising pneumonia from an oesophagopleural fistula, an abscess, and a migrated stent. She required a left thoracotomy, abscess drainage, decortication, lung wedge resection, muscle flap reinforcement, and a PEG tube for feeding. At ten-month follow-up, oesophageal healing was confirmed on endoscopy, the PEG tube was removed, and she was maintaining a regular diet. She was advised to permanently discontinue GLP-1 receptor agonists.

Why dose titration matters

GLP-1 receptor agonists slow gastric emptying. That delayed motility is part of the therapeutic mechanism, reducing appetite and caloric intake, but it also drives the class-wide gastrointestinal side-effect profile: nausea, vomiting, and constipation. These effects are dose-dependent and most pronounced during the first weeks after each dose increase. The standard semaglutide prescribing schedule starts at 0.25 mg weekly and escalates over 16 to 20 weeks to the maintenance dose of 2.4 mg. Skipping that ramp, as happened in this case, exposes the patient to the full gastrointestinal burden of the top dose without physiological adaptation.

The same dose-dependent GI pattern applies across the incretin class. Tirzepatide and liraglutide carry similar titration requirements for the same reason. When clinicians or patients skip steps in the escalation, the risk of severe nausea and vomiting rises substantially. In the STEP and SURMOUNT programmes, the titration protocols kept treatment-emergent vomiting manageable in most participants, but real-world adherence to those schedules is inconsistent.

The broader GI safety signal

This case does not change the overall benefit-risk profile of GLP-1 receptor agonists, but it does illustrate the downstream consequences of their most common side effect. A 2023 cohort study published in JAMA by Sodhi and colleagues found that GLP-1 agonist use for weight loss was associated with increased risks of gastroparesis (hazard ratio 3.67) and bowel obstruction (hazard ratio 4.22) compared with bupropion-naltrexone^[3]. The Aubrey, Benner, and Lam case report adds oesophageal perforation to the spectrum of rare but serious GI complications that clinicians should consider, particularly when patients present with persistent or severe vomiting.

What we do not yet know

This is a single case report. It establishes biological plausibility (GLP-1-induced vomiting leading to oesophageal rupture) but cannot establish incidence. There are no FAERS signal analyses or large-cohort studies specifically examining the association between GLP-1 receptor agonist use and oesophageal perforation. Whether the risk is confined to patients who skip dose titration, or extends to those who follow the standard escalation schedule, is unknown. A PubMed search for GLP-1 agonist esophageal perforation returns only this single case report as of June 2026.

It is also unclear whether certain patient subgroups face higher risk. Conditions that weaken the oesophageal wall, such as eosinophilic oesophagitis, previous oesophageal surgery, or chronic acid reflux with Barrett's changes, could theoretically lower the threshold for perforation during forceful vomiting. None of these were reported in this patient, but they have not been studied in the GLP-1 population either.

Practical takeaway

The authors of the case report recommended that clinicians maintain a high index of suspicion for oesophageal perforation in GLP-1 RA patients who present with severe vomiting followed by chest pain, particularly if the drug was restarted at a high dose. For patients considering or currently using these medications, the standard advice applies: follow the prescribed dose-escalation schedule and report persistent vomiting to your prescriber promptly. Do not restart a GLP-1 agonist at a high dose without medical guidance. For country-specific prescribing details, see the semaglutide regulation pages.