Pancreatic Mucinous Cystic Neoplasms Following GLP-1 Receptor Agonists Use: A Report of Two Cases with Literature Review.

INTRODUCTION AND IMPORTANCE: Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is increasingly used for glycemic control, weight loss, and cardiovascular risk reduction. While GLP-1 RAs are commonly associated with acute pancreatitis, emerging reports suggest a possible association with pancreatic cystic lesions, even in patients without typical risks factors such as alcohol, gallstones, or hereditary syndromes. CASE PRESENTATION: We present two cases of middle-age female patients without prior compline or pancreatic disease who developed large distal pancreatic mucinous cystic neoplasms following GLP-1 Ras use. Both underwent imaging and aspiration, which revealed elevated carcinoembryonic antigen (CEA) levels. Surgical management consisted of distal pancreatectomy and splenectomy. Pathology confirmed MCN with no malignancy. Both patients had uneventful recovery. DISCUSSION: These two cases suggest a possible association between GLP-1 receptor agonists, and the development of pancreatic mucinous cystic neoplasms (MCNs) in patients without prior pancreatic disease or conventional risk factors. While causality cannot be established, the temporal relationship, absence of alternative etiologies, and supportive literature suggest a possible drug-related effect. Preclinical studies have implicated GLP-1 RAs in pancreatic ductal hyperplasia and cyst formation, and recent clinical reports reinforce these findings. As semaglutide use expands, clinicians should be vigilant for structural pancreatic changes, and further studies are warranted to elucidate underlying mechanisms and clinical implications. CONCLUSION: These cases raise concern regarding a potential association between semaglutide therapy and mucinous cystic neoplasms. Increased vigilance and further observational studies are warranted to evaluate this potential adverse effect.