S6351 Post-Fundoplication Dumping Syndrome Successfully Managed With Tirzepatide: A Case Report

Introduction: Dumping syndrome (DS), characterized by rapid gastric emptying leading to gastrointestinal (GI) and vasomotor symptoms, complicates about 5-10% of bariatric surgeries and rarely occurs after fundoplication. The mainstay of therapy remains dietary and lifestyle modifications to delay gastric emptying. Pharmacotherapy for refractory DS has had varying responses. We present a case of post-fundoplication DS treated with tirzepatide. Case Description/Methods: A 36-year-old woman with a history of obesity, hiatal hernia (HH), and refractory reflux disease, status post HH repair with Toupet fundoplication, presented with abdominal discomfort, diarrhea, and postprandial fatigue for 4 years. Symptoms started about 6 months post-surgery. A nuclear medicine gastric emptying study revealed accelerated gastric emptying (50% emptying at 30.1 minutes, 90% at 54 minutes), consistent with DS. Given her concurrent obesity, she was started on weekly tirzepatide to facilitate weight loss. Interestingly, tirzepatide resulted in the resolution of her DS symptoms. Upon achieving her target weight, the patient's tirzepatide was tapered and discontinued. Discontinuation of tirzepatide led to relapse of her DS symptoms. Discussion: Post-fundoplication DS is an underrecognized disease. The pathophysiology of DS is a cascade initiated by rapid presentation of large hyperosmolar contents to the small intestine (SI), resulting in fluid shifts from the intravascular to the intraluminal compartments, leading to early vasomotor and GI symptoms. Secondarily, distension of the SI leads to enhanced release of GI hormones, such as vasoactive agents and incretins such as glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP). The high incretin levels mediate insulin secretion and subsequent hypoglycemia. Ironically, while an exaggerated GLP-1 and GIP response is considered a key factor in DS, there is growing interest in the off-label use of GLP-1 agonists in treatment-refractory DS. Theoretically, tirzepatide should exacerbate DS given its role in the secondary cascade. However, practically, given the consistent plateau of GLP1 and GIP agonism and resultant delay in gastric emptying, there is reduced hyperosmolar loading of the SI, resulting in symptomatic improvement. This has been demonstrated in a few reports. Our case highlights the need to recognize post-fundoplication DS, and the use of incretin-based therapies like tirzepatide for refractory DS.