Are there concerns with pancreatic cysts and liver adenoma when initiating Glucagon-like peptide-1 (GLP-1) receptor agonists?

From the Guidelines

Starting GLP-1 receptor agonists with pancreatic cysts and liver adenomas requires caution but is not absolutely contraindicated, and the benefits often outweigh the risks, especially with regular monitoring and personalized recommendations from specialists 1. When considering the initiation of GLP-1 receptor agonists, such as semaglutide or liraglutide, in patients with pancreatic cysts and liver adenomas, several factors must be taken into account to ensure safe and effective treatment.

Key Considerations

• Theoretical concerns exist regarding the potential for GLP-1 medications to stimulate pancreatic cell growth, which could affect cyst progression 1.
• Regular monitoring with imaging (typically every 6-12 months) is crucial if these medications are started.
• For liver adenomas, while there's less direct concern with GLP-1 medications, significant weight loss could impact liver metabolism.
• Baseline imaging of both the pancreas and liver should be obtained before starting treatment.
• Discussion with gastroenterology or hepatology specialists is recommended for personalized advice.

Recommendations for Treatment Initiation

• Start with lower doses of the GLP-1 medication and gradually increase while monitoring for concerning symptoms.
• Schedule regular follow-up imaging studies to monitor both conditions while on treatment.
• The decision to start GLP-1 receptor agonists should be based on an individualized assessment of the benefits and risks, considering the patient's specific health status and the potential impact on their quality of life and morbidity 1.

From the FDA Drug Label

Acute Pancreatitis: Post-marketing reports with exenatide, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis. Discontinue exenatide promptly. Exenatide should not be restarted. Consider other antidiabetic therapies in patients with a history of pancreatitis. (5. 2) Has not been studied in patients with a history of pancreatitis Consider other antidiabetic therapies in patients with a history of pancreatitis. (1)

Concerns with Pancreatic Cyst and Liver Adenoma

• The FDA drug label for exenatide 2 mentions acute pancreatitis as a warning and precaution, which may be a concern for patients with pancreatic cysts.
• There is no direct information in the drug label regarding liver adenomas.
• However, considering the potential risk of acute pancreatitis, it is recommended to exercise caution when starting GLP-1 therapy, such as exenatide, in patients with pancreatic cysts.
• It is also recommended to consider alternative antidiabetic therapies in patients with a history of pancreatitis or pancreatic cysts.
• For liver adenomas, there is no clear guidance in the provided drug labels, and therefore, no conclusion can be drawn.

From the Research

Pancreatic Cyst and Liver Adenoma Concerns

• The presence of pancreatic cysts and liver adenoma may raise concerns when starting GLP-1 receptor agonists, but the current evidence does not suggest a significant increase in risk of pancreatitis or pancreatic cancer associated with GLP-1 RAs 3, 4.
• Pancreatic cysts are common and can be incidentally identified, with the majority being benign, but some types can contain cancer or have malignant potential 5.
• The management of pancreatic cysts can be confusing due to multiple guidelines with varying recommendations, but high-risk features such as presence of a mural nodule or solid component, dilation of the main pancreatic duct, pancreatic cyst size ≥3-4 cm, or positive cytology on pancreatic cyst fluid aspiration should be considered 6.

GLP-1 Receptor Agonists and Pancreatic Risk

• A study found that the use of GLP-1 RAs did not increase the risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes mellitus (T2DM) in the United States 3.
• Another study found that GLP-1 RA showed no association with pancreatitis and pancreatic cancer, but data on pancreatic cancer are too scarce to draw any conclusion 4.
• Selection criteria for operative and nonoperative management of pancreatic cysts include symptoms, cyst size, solid component, and septations, and selected patients with cystic lesions of the pancreas may be safely followed radiographically 7.

Liver Adenoma Considerations

• There is limited evidence available on the specific interaction between GLP-1 receptor agonists and liver adenoma, and further research is needed to fully understand any potential risks or concerns.
• However, the current evidence on GLP-1 RAs and pancreatic risk does not suggest a significant increase in risk of pancreatitis or pancreatic cancer, which may be relevant when considering the use of GLP-1 RAs in patients with liver adenoma 3, 4.