Is Glucagon-like peptide-1 (GLP-1) associated with pancreatitis?

From the Guidelines

GLP-1 receptor agonists (GLP-1 RAs) should be used with caution in patients with a history of pancreatitis, and those with risk factors for pancreatitis should be monitored closely, as the risk of pancreatitis associated with GLP-1 RAs is a significant concern. Patients with a history of pancreatitis should generally avoid these medications, and those with risk factors for pancreatitis (gallstones, heavy alcohol use, hypertriglyceridemia) should be monitored closely 1. Common GLP-1 RAs include semaglutide (Ozempic, Wegovy), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), and tirzepatide (Mounjaro, Zepbound). If a patient on a GLP-1 RA develops severe abdominal pain, especially with nausea and vomiting, they should seek immediate medical attention and the medication should be discontinued 1. Diagnosis involves measuring pancreatic enzymes (amylase, lipase) and imaging. The mechanism behind GLP-1-associated pancreatitis likely involves increased pancreatic enzyme production, ductal pressure changes, and possibly direct effects on pancreatic cells. While the absolute risk is low (approximately 0.1-0.2%), healthcare providers should discuss this risk with patients before starting therapy and remain vigilant for symptoms, especially during the first months of treatment when risk appears highest 1.

Some key points to consider when prescribing GLP-1 RAs include:

• Contraindications: history of serious hyper-sensitivity reaction to the drug, personal or family history of medullary thyroid cancer, or multiple endocrine neoplasia type 2 1
• Cautions: use with caution in patients with history of pancreatitis, severe renal impairment or end-stage renal disease, and history of gastroparesis 1
• Dose modifications: up-titrate slowly to reduce nausea and vomiting, discontinue if pancreatitis is suspected and do not restart if pancreatitis is confirmed 1

Overall, while GLP-1 RAs can be effective in managing type 2 diabetes, the risk of pancreatitis associated with these medications must be carefully considered and monitored. Healthcare providers should prioritize the safety of their patients and use GLP-1 RAs judiciously, taking into account the potential risks and benefits 1.

From the Research

GLP-1 Associated Pancreatitis

• The association between GLP-1 receptor agonists and the risk of pancreatitis is a complex issue, with some studies suggesting a potential link and others finding no increased risk 2, 3, 4.
• A study published in the Journal of Clinical Medicine found that the use of GLP-1 receptor agonists did not increase the risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes mellitus in the United States 2.
• In contrast, a study published in the Journal of Diabetes and Metabolic Disorders found that the risk of pancreatitis associated with GLP-1 agonists is dose-dependent, with higher cumulative doses increasing the risk of developing pancreatitis 3.
• A systematic review and meta-analysis of randomized placebo-controlled trials found no evidence that treatment with GLP-1 receptor agonists increases the risk of acute pancreatitis in patients with type 2 diabetes 4.
• Another study published in Gaceta Sanitaria found no risk differences for acute pancreatitis or biliary disease in patients treated with GLP-1 receptor agonists compared to those treated with sodium-glucose cotransporter 2 inhibitors 5.

Key Findings

• The risk of pancreatitis associated with GLP-1 receptor agonists may be influenced by the dose and duration of treatment 3.
• GLP-1 receptor agonists may have different efficacy and safety profiles, and selection of the most appropriate treatment for individual patients is important 6.
• Close monitoring of potential adverse events is warranted to ensure patient safety, despite the lack of increased risk of gastrointestinal events found in some studies 5.

Study Results

• A study published in the Journal of Clinical Medicine found that the lifetime risk of developing pancreatitis in patients on GLP-1 receptor agonists was lower (0.3% vs. 0.4%, p < 0.001) compared to those not on GLP-1 receptor agonists 2.
• A study published in the Journal of Diabetes and Metabolic Disorders found that patients with a high cumulative dose of GLP-1 agonist were associated with a higher risk of developing drug-induced pancreatitis, with a statistically significant odds ratio 3.