Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist widely prescribed for type 2 diabetes mellitus and obesity, is generally well tolerated but can be associated with gastrointestinal adverse effects and, rarely, pancreatitis. As its use grows, clinicians must remain aware of potential complications, particularly in patients with additional risk factors. We report the case of a 57-year-old woman with diabetes, hypertension, and hyperlipidemia who presented with acute severe epigastric pain and persistent vomiting shortly after consuming a large, fatty meal. She had been receiving semaglutide for several months. Laboratory studies showed marked leukocytosis, hyperglycemia with an anion gap metabolic acidosis, and a lipase level exceeding 3000 U/L. CT imaging demonstrated acute interstitial edematous pancreatitis with peripancreatic fluid and early concern for necrosis. She was treated conservatively with aggressive intravenous hydration, bowel rest, electrolyte repletion, and analgesia. Her condition improved with supportive care, and she was discharged with close outpatient follow-up. This case highlights the importance of recognizing pancreatitis as a possible multifactorial complication in patients using GLP-1 receptor agonists. This case highlights the need for clinicians to maintain awareness of pancreatitis as a potential adverse effect in patients receiving semaglutide, especially those with additional risk factors such as biliary pathology or dietary triggers. As the use of GLP-1 receptor agonists continues to grow, careful assessment of abdominal symptoms and early recognition of pancreatic inflammation are essential for optimizing outcomes and guiding safe prescribing practices.
