Glucagon-like peptide-1 receptor agonists as adjunctive therapy in refractory hypertriglyceridemia following recurrent pancreatitis

A 39-year-old Chinese man was first evaluated at a multidisciplinary metabolic dysfunction–associated liver disease clinic following 6 episodes of hypertriglyceridemia-induced pancreatitis over 9 years despite maximal therapy with statins, fibrates, and omega-3 fatty acids. Peak triglycerides reached 2329 mg/dL (Système International [SI]: 26.3 mmol/L; reference range, <177 mg/dL [SI: <2 mmol/L]). Comorbidities included poorly controlled diabetes, recurrent hypoglycemia, and steatotic liver disease with moderate fibrosis. Despite historical safety concerns regarding glucagon-like peptide-1 receptor agonists in prior pancreatitis, semaglutide was cautiously initiated. This achieved sustained triglyceride normalization to 213 mg/dL (SI: 2.4 mmol/L), weight loss, glycemic improvement, hypoglycemia resolution, improved liver elastography parameters, and insulin cessation without pancreatitis recurrence. This case demonstrates that glucagon-like peptide-1 receptor agonists warrant consideration in treatment-resistant hypertriglyceridemia with prior pancreatitis when conventional therapy fails, challenging traditional contraindications in carefully selected patients under multidisciplinary care.