Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are essential in managing type 2 diabetes mellitus, promoting glucose regulation, weight reduction, and cardiovascular protection. Here, we report a unique case of semaglutide-induced pancreatitis complicated by distributive shock and death after four years of use. A 74-year-old male with type 2 diabetes, atrial fibrillation, coronary artery disease, and obesity (BMI 31.7) presented with severe epigastric pain and was diagnosed with severe pancreatitis. He reported no recent alcohol, drug use, or abdominal trauma. His workup showed normal triglyceride and calcium levels, and abdominal ultrasound was negative for gallstones or choledocholithiasis. He had been on semaglutide for four years, with a dose increase from 0.25 to 0.5 mg weekly about four weeks prior to admission, which was associated with worsening side effects such as severe nausea and constipation. He was admitted to the intensive care unit for severe pancreatitis, which was complicated by distributive shock requiring vasopressors, renal failure requiring continuous renal replacement therapy, Acute respiratory distress syndrome (ARDS) requiring intubation, and subsequently, cardiac arrest. In this case, the patient developed severe acute pancreatitis leading to death after four years of GLP-1RA use, with a dose increase occurring four weeks prior to admission. The absence of typical risk factors suggests a potential link between long-term use and dose changes of GLP-1RAs and severe pancreatitis.
