Abstract Disclosure: G. Arevalo: None. S. Gra Menendez: None. D. Soliman: None. R.J. Galindo: Consulting Fee; Self; Novo Nordisk, Eli Lilly & Company, Sanofi, Bayer, Inc., Boehringer Ingelheim, Pfizer, Inc., Abbott Laboratories. Grant Recipient; Self; National Institute of Diabetes and Digestive and Kidney Diseases (2P30DK111024), National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123384). Other; Self; Novo Nordisk, Eli Lilly & Company, Dexcom. Background: Late dumping syndrome, characterized by postprandial hyperinsulinemic hypoglycemia (PHH), represents a complex clinical challenge in post-bariatric patients. GLP-1 receptor agonists are being explored as an effective therapeutic option. Clinical Case: A 47-year-old overweight (BMI of 29.86 kg/m²) woman, with a medical history of scleroderma and esophageal dysmotility, underwent a gastric sleeve gastrectomy later requiring conversion to Roux-en-Y gastric bypass to improve esophageal motility. Eleven months post-bypass, she began experiencing recurrent episodes of hypoglycemia (venous glucose 49-70 mg/dL, n >70 mg/dL) accompanied by sweating, palpitations, drowsiness, and weakness. Initial tests were consistent with postprandial hyperinsulinemic hypoglycemia: serum insulin (13.5 µIU/mL, n < 3 µIU/mL), and c-peptide (4.1 ng/mL, n < 0.6 ng/mL). The Sigstad score and the Arts dumping severity score were positive for late dumping syndrome with a score of 26 and 14, respectively. During glucagon administration, the patient's blood glucose level increased by up to 50 mg/dL within 10 minutes of administration. Both sulfonylurea screening and insulin antibody tests were negative. Real-time CGM measurements showed patterns of postprandial hyperglycemic peaks, up to 160-180 mg/dL (n <140 mg/dL), approximately 30 to 60 min after meals, followed by rapidly declining glucose (1-2 hours later), resulting in hypoglycemic events as low as 49 mg/dL. Initial management with dietary changes and pharmacological treatment was unsuccessful due to poor medication tolerability of acarbose and diazoxide, and low adherence to the prescribed diet due to her esophageal dysmotility. The CGM patterns and symptom presentation raised suspicion that late dumping syndrome was triggered by rapid hyperglycemic responses after oral ingestions of typical meals, resulting in the desynchronization of hormonal responses (insulin and GLP-1), and post-prandial hypoglycemia. Hence, the consideration for a GLP-1 receptor agonist emerged. A weekly subcutaneous injection of a long-acting GLP-1 receptor agonist, semaglutide 0.25 mg exhibited marked improvement in her glycemic profile: fewer episodes of postprandial hyperglycemia, and the subsequent descents in blood glucose were less pronounced. The patient demonstrated a favorable response with no severe hypoglycemic episodes reported during a follow-up period of three months. Conclusion: This is the first case to demonstrate semaglutide's efficacy as a standalone treatment for PHH in post-bariatric patients. In this case, semaglutide effectively controlled glycemia and improved the patient's quality of life, presenting a promising therapeutic option for such complex cases. Presentation: 6/1/2024