Tirzepatide for refractory post-fundoplication dumping syndrome: A case report

Table 1 Mechanism of action of pharmacotherapies used for dumping syndrome

Pharmacotherapy	Mechanism of action in dumping syndrome
α-glucosidase inhibitor (e.g., acarbose)	Competitively inhibits intestinal α-glucosidases, which delays the breakdown of complex carbohydrates into monosaccharides. This reduces glucose absorption, thereby decreasing postprandial glucose spikes and the subsequent effects of hyperinsulinemia
Uncooked cornstarch	A complex carbohydrate with a low glycemic index that is slowly digested and absorbed offers a gradual release of glucose. This supports maintaining euglycemia and prevents post-meal hypoglycemic episodes
Calcium channel blockers (e.g., nifedipine)	Inhibit voltage-gated calcium channels on pancreatic β-cells, reducing calcium influx inside the cell. This suppresses insulin secretion and helps reduce hyperinsulinemic responses to post-meal glucose elevations
Nondiuretic benzothiadiazine derivative (diazoxide)	Activates ATP-sensitive potassium channels on pancreatic β-cells, causing membrane hyperpolarization. This action inhibits voltage-dependent calcium channels, reducing insulin secretion and countering hyperinsulinemic hypoglycemia
Somatostatin analogues (e.g., octreotide)	Binds to somatostatin receptors, inhibiting insulin secretion and other gastrointestinal hormones like incretins. This decreases postprandial insulin release and slows gastric emptying, thereby preventing hypoglycemia
Avexitide	Glucagon-like peptide receptor (GLP-1) antagonists that reduce postprandial insulin and GLP-1 secretion and increase glucagon

GLP-1: Glucagon-like peptide-1.

Table 2 Comprehensive comparison of our case and published dumping syndrome cases treated with glucagon-like peptide-1 analogs

Ref.	Age/gender	Surgery type	Timing of symptom onset	Primary symptoms	Documented hypoglycemia	Failed prior therapies	Incretin therapy used	Initial dose	Maximum dose	Symptom response	Response to discontinuation	Follow-up duration
Our case	36/female	Toupet 270° fundoplication	6 months post-operation	Hunger pain, diarrhea, fatigue	No	Dietary modification	Tirzepatide	2.5 mg weekly	5 mg weekly	Complete resolution	Symptom recurrence	7 months before taper
Chiappetta and Stier[10]	52/female	Toupet fundoplication	12 months post-operation	Palpitations, nausea, sweating	Yes (nadir 35 mg/dL)	Dietary modification	Liraglutide	0.6 mg daily	1.2 mg daily	Significant improvement	Not attempted	Not specified
Ding et al[11]	53/male	Distal gastrectomy	16 months post-operation	Palpitations, sweating, dizziness	Yes (nadir 1.8 mmol/L)	Acarbose, diet	Beinaglutide	0.1 mg twice daily	0.1 mg twice daily	Complete resolution	Not attempted	1 month
Stortz and Lawler[12]	46/female	Sleeve gastrectomy	Approximately 8 months post-operation	Bloating, diarrhea, confusion	Yes (30-50 mg/dL)	Dietary modification	Tirzepatide	2.5 mg weekly	5 mg weekly	Complete resolution	Not reported	1.5 years

Table 3 Timeline of clinical course from symptom onset through tirzepatide treatment and follow-up

Time point	Clinical phase	Key clinical & diagnostic details	Surgical context	Tirzepatide dose	Symptom status	BMI (kg/m2)
4 years prior	Index surgery	Laparoscopic paraesophageal herniorrhaphy for hiatal hernia and reflux	Toupet 270° fundoplication	N/A	Reflux symptoms present	36
Approximately 3.5 years prior (6 months post-procedure)	Symptom onset	Postprandial abdominal discomfort, diarrhea, generalized weakness, hunger pain; reflux improved	Post-fundoplication	N/A	DS symptoms (8-9/10)	36
3 months prior	Initial evaluation	Persistent symptoms despite dietary modification and proton pump inhibitor therapy	Post-fundoplication	N/A	DS symptoms (8-9/10)	36
2 months prior	Diagnostic work-up	CT abdomen/pelvis unremarkable; endoscopy with wireless pH showed intact fundoplication and reduced acid exposure (1.6%); gastric emptying study confirmed rapid emptying	Post-fundoplication	N/A	DS symptoms (8-9/10)	36
Month 0	Diagnosis & treatment initiation	Dumping syndrome diagnosed; tirzepatide initiated for obesity management	Post-fundoplication	2.5 mg weekly	Improving DS symptoms (6/10)	36
Month 2 (week 8)	Dose escalation	Dose increased due to good tolerability and partial symptom response	Post-fundoplication	5 mg weekly	Minimal DS symptoms (2/10)	34-35
Months 3-7	Maintenance phase	Continued therapy with progressive weight loss	Post-fundoplication	5 mg weekly	Minimal DS symptoms (1-2/10)	26-34
Month 7	Target BMI achieved	Approximately 50-lb weight loss achieved; target BMI reached	Post-fundoplication	5 mg weekly	Minimal DS symptoms (1-2/10)	26
Months 8-9	Dose tapering & discontinuation	Gradual dose reduction and discontinuation; symptoms gradually recurred despite stable weight	Post-fundoplication	5 mg to 2.5 mg to 0 mg	Progressive DS symptoms (2-6/10)	26 (stable)
Month 9	Post-discontinuation reassessment	Repeat endoscopy unremarkable; full symptom recurrence with stable BMI	Post-fundoplication	0 mg	Severe DS symptoms (8/10)	26.5 (stable)
Month 11	Treatment reinitiation	Tirzepatide restarted at lower maintenance dose	Post-fundoplication	2.5 mg weekly	Improving DS symptoms (2-6/10)	26 (stable)
Months 12-20	Follow-up/sustained remission	Sustained symptom resolution at 3- and 6-month follow-up; no adverse effects	Post-fundoplication	2.5 mg weekly	Minimal DS symptoms (1-2/10)	26 (stable)

BMI: Body mass index; N/A: Not available; DS: Dumping syndrome; CT: Computed tomography.