(1042) Semaglutide-Induced Acute Pancreatitis Leading to Death After Four Years of Use

Introduction: Glucagon-like peptide 1 (GLP-1) is a hormone that enhances insulin levels when glucose is ingested. GLP-1 receptor agonists (GLP-1RAs) are essential in managing type 2 diabetes mellitus, promoting glucose regulation, weight reduction, and cardiovascular protection. While GLP-1RAs are associated with acute pancreatitis, studies show mixed results regarding pancreatic adverse events. Those that demonstrate an association typically involve short-term use. Here, we report a unique case of Semaglutide-induced pancreatitis complicated by distributive shock and death after four years of use.

Description: 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 imaging was negative for gallstones or choledocholithiasis. He had been on Semaglutide for 4 years, with a dose increase from 0.25 to 0.5 mg weekly about 4 weeks prior to admission, which was associated with worsening side effects. 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, ARDS requiring intubation, and subsequently, cardiac arrest.

Discussion: GLP-1RAs have been linked to acute pancreatitis, potentially due to receptor activation causing pancreatic cell proliferation and duct blockage. Some studies have shown a higher incidence of pancreatitis with Semaglutide compared to other GLP-1RAs, and some case reports have documented severe pancreatitis following Semaglutide use. However, other studies have presented mixed results, with varying rates of pancreatitis between Semaglutide and placebo groups. In our case, the patient developed severe acute pancreatitis leading to death after 4 years of GLP-1RA use, with a dose increase occurring 4 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.