P2174 - Comparative Risk of Pancreatic Pseudocyst Among Users of GLP-1 RAs: Findings From a Large-Scale EHR-Based Study

Lina AlQirem, MD¹, Adalberto Guzman, MD², Suria Devarapalli, DO¹, Ronald Blanco Montecino, MD³, Sumant Inamdar, MD¹
1University of Arkansas for Medical Sciences, Little Rock, AR; 2University of Arkansas, Little Rock, AR; 3St. Barnabas Hospital, New York, NY

Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in the management of type 2 diabetes mellitus, weight loss due to their favorable glycemic and cardiovascular profiles. However, concerns regarding pancreatic safety have been raised, particularly in relation to acute pancreatitis. Albeit studies have investigated the incidence of pancreatitis associated with GLP-1 RA use, the specific risk of pancreatic pseudocyst formation—a complication of pancreatitis—remains unclear. Current safety data on GLP-1 RAs focuses on the incidence of acute pancreatitis, not pseudocyst rates. This gap highlights the need for targeted research to define the risk of pancreatic pseudocyst in this specific patient population.

Methods: A retrospective cohort study utilizing TriNetX Research Network, a federated cloud-based database comprising de-identified electronic health records from healthcare institutions across the United States. Adult patients 18- 90 years with at least 6 months of GLP-1 RA exposure prescribed for diabetes, obesity, PCOS, metabolic syndrome or weight loss. Any prior diagnosis of chronic pancreatitis or pancreatic pseudocyst (ICD-10-CM codes K86.1, K86.3) were excluded. Pancreatic pseudocyst formation following GLP-1 RA initiation was identified with ICD-10 codes.

Results: Among 2,666,800 patients, the overall risk of developing a pancreatic pseudocyst was low, with notable variation by specific medication. Tirzepatide was associated with the lowest observed risk at 0.143% (737 cases among 516,978 patients), followed by semaglutide at 0.334% (3,817/1,142,264), dulaglutide at 0.605% (3,243/536,042), liraglutide at 0.723% (2,479/342,996), lixisenatide at 0.755% (114/15,097), exenatide at 0.935% (990/105,875), and albiglutide at 0.941% (71/7,548). Patients on newer agents (semaglutide, tirzepatide) demonstrated a substantially lower risk of pseudocyst formation compared to those on older agents (albiglutide, exenatide). These findings suggest that GLP-1 RA use is associated with a low absolute risk of pancreatic pseudocyst formation, with risk estimates ranging from 0.143% to 0.941% depending on the specific agent.

Discussion: In this nationwide cohort study, the risk of pancreatic pseudocyst formation following GLP-1 receptor agonist use was low across all agents studied. While absolute risk varied slightly by medication, newer GLP-1 RAs were associated with the lowest rates. These findings support the pancreatic safety profile of GLP-1 RAs in adults.

Disclosures:
Lina AlQirem indicated no relevant financial relationships.
Adalberto Guzman indicated no relevant financial relationships.
Suria Devarapalli indicated no relevant financial relationships.
Ronald Blanco Montecino indicated no relevant financial relationships.
Sumant Inamdar indicated no relevant financial relationships.

Lina AlQirem, MD¹, Adalberto Guzman, MD², Suria Devarapalli, DO¹, Ronald Blanco Montecino, MD³, Sumant Inamdar, MD¹. P2174 - Comparative Risk of Pancreatic Pseudocyst Among Users of GLP-1 RAs: Findings From a Large-Scale EHR-Based Study, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.