(276) The Shadow of Semaglutide: A Fatal Case of Drug-Induced Pancreatitis

Introduction: Pancreatitis is an inflammatory condition of the pancreas that can cause severe morbidity and mortality — known to be triggered by various factors, including medications. Here, we present a case of severe pancreatitis, for which the potential suspect of the etiology is semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA) for type 2 diabetes mellitus (T2DM), resulting in the patient's death.

Description: A 73-year-old male with a history of (T2DM) on semaglutide presented with a one-day history of acute mid-epigastric abdominal pain, nausea, and vomiting. Initial laboratory results showed a white blood cell count of 21.90 x 10^3/uL, hemoglobin of 17.9 g/dL, potassium level of 6.7 mmol/, bicarbonate level of 20 mEq/L, anion gap at 18 mmol/L, creatinine of 1.92 mg/dL, and fasting blood glucose of 430 mg/dL. The lipase level was at >10,070 U/L, and venous lactate was 8.00 mmol/L. Fluid resuscitation was initiated along with diabetic ketoacidosis management. Despite aggressive treatment, the patient's condition worsened, showing persistent metabolic acidosis, elevated inflammatory markers, and deteriorating renal function. During hospitalization, he developed multi-organ failure, including respiratory failure requiring mechanical ventilation, refractory hypotension despite maximized vasopressor support, and progressive renal failure needing continuous renal replacement therapy. Despite maximal supportive care, the patient eventually passed away.

Discussion: Our patient was on semaglutide for one year. Notably, the patient's semaglutide dose was increased two months before his presentation. The exclusion of typical causes of pancreatitis, such as recent ethanol use, along with negative laboratory workup for hypercalcemia, hypertriglyceridemia, and imaging negative for biliary pathology, points towards subcutaneous semaglutide as the likely cause of AP. Despite the Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) trial indicating no increased risk of AP with semaglutide, a clear link between the two remains controversial. The pathogenesis of drug-induced pancreatitis remains unclear, emphasizing the need for further research. This case underscores the importance of monitoring patients on GLP-1 RAs for new-onset gastrointestinal complications.