Severe reflux oesophagitis caused by repeated vomiting due to glucagon-like peptide-1 receptor agonist

Description

A woman in her 70s with type 2 diabetes mellitus (DM) and class 3 obesity (body mass index (BMI): 51.1 kg/m²) had been treated with a weekly 0.25 mg of semaglutide injection for DM by a physician in another hospital. She was often confined to bed because of bilateral knee osteoarthritis. Due to the favourable progression of her condition, the dosage of semaglutide was increased to 0.5 mg; however, frequent vomiting occurred in 1 week. Although vomiting was persistent, the semaglutide treatment was continued because a reduction in body weight was achieved (BMI: 42.2 kg/m²). Six months later, she was unable to consume food and was subsequently referred to our hospital and admitted due to exacerbation of vomiting and epigastric pain.

CT revealed diffuse oesophageal wall thickening. Oesophagogastroduodenoscopy revealed a very severe and giant ulcer from the upper thoracic to the abdominal oesophagus (figure 1).

Figure 1. Endoscopic findings on admission. Severe ulceration of the entire circumference was found (A: oesophageal junction, B: middle thoracic oesophagus) and several shallow transverse ulcers (arrow marks) in the upper thoracic oesophagus (C) were detected.

We considered the following differential diagnoses: malignant disorders, drug-induced injury by bisphosphonates and dabigatran etexilate methanesulfonate, viral infection by cytomegalovirus and herpesviruses, and severe gastro-oesophageal reflux disease (GERD). She was not taking any medications known to cause drug-induced oesophagitis, such as bisphosphonates or dabigatran etexilate mesylate. Based on the patient’s clinical course and endoscopic findings, we diagnosed her with severe GERD caused by repeated vomiting due to semaglutide. Semaglutide treatment was discontinued and proton pump inhibitors (PPIs) and mucoprotective agents were administrated. After 2 weeks, clinical manifestations gradually improved and she was able to resume oral intake. On endoscopic evaluation 1 month after treatment onset, the severe oesophageal ulcer was healed without stenosis (figure 2).

Figure 2. Endoscopic findings 1 month after semaglutide discontinuation and the initiation of proton pump inhibitors and mucoprotective agents. The oesophagus was tightly covered with mucosa and scarred without causing stenosis (A: oesophageal junction, B: middle thoracic oesophagus, C: upper thoracic oesophagus).

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as semaglutide have been approved for the treatment of patients with type 2 DM and obesity. It is well-known that the adverse effects include hypoglycaemia, pancreatitis, anorexia, vomiting and diarrhoea. Considering the pathophysiology of this case, it is estimated that the administration of semaglutide to patients with high BMIs who frequently recline could potentially promote GERD due to decreased gastric motility associated with semaglutide use. Delayed gastric emptying by GLP-1RAs significantly reduces postprandial glucose levels in type 2 DM¹ but may also cause nausea and vomiting. Most gastrointestinal events associated with semaglutide occur within the first month² and are dose-dependent.³ The reported nausea and vomiting rates are 43.9% and 24.5%, respectively.⁴ Noguchi et al⁵ reported elevated risks of GERD-like symptoms with GLP-1RAs (ROR 5.61, IC 2.17). Shu et al⁶ found semaglutide-related serious and non-serious GERD incidence rates of 2.64% and 3.28%, respectively. However, diagnoses were largely symptom-based, and endoscopic confirmation was often lacking. To the best of our knowledge, this is the first endoscopically confirmed case of severe GLP-1RA-induced GERD. In patients receiving GLP-1RAs therapy who develop so-called red-flag symptoms such as persistent vomiting or epigastric pain, clinicians should promptly investigate potential underlying causes through methods that include endoscopy, with a high index of suspicion for severe GERD. As demonstrated in the present case, the indiscriminate use of semaglutide may not only exacerbate symptoms but also lead to complications such as oesophageal stricture; therefore, it must be strictly avoided. Several studies have reported that risk factors for the development of new-onset GERD include increasing age, female sex, elevated BMI, lower educational attainment and a history of tobacco use.^{7 8} It may be advisable to administer antacids, such as PPIs or potassium-competitive acid blockers, prophylactically when prescribing GLP-1RAs to patients with these risk factors.

Learning points.

• Frequent vomiting is a well-known adverse effect of glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) and it can cause severe gastro-oesophageal reflux disease.

• Semaglutide was found to carry the highest risk of nausea and vomiting among the GLP-1 RAs, with the majority of gastrointestinal events occurring within the first month of its initiation. Furthermore, the adverse effects of semaglutide—such as vomiting—have been reported to increase in a dose-dependent manner.

• If the red-flag symptoms associated with GLP-1RAs (such as persistent vomiting) are observed, these agents should not be continued indiscriminately. Instead, prompt investigation (including endoscopic evaluation of the upper gastrointestinal tract) should be performed and appropriate treatment should be instituted promptly.