Does semaglutide (glucagon-like peptide-1 (GLP-1) receptor agonist) cause pancreatitis?

From the Guidelines

Semaglutide has been associated with a small increased risk of pancreatitis, though this side effect is rare, and patients should be aware of this potential risk but not necessarily avoid the medication solely for this reason. The risk appears to be higher in patients with a history of pancreatitis or gallbladder disease. If you're taking semaglutide and experience severe abdominal pain that may radiate to your back, nausea, vomiting, or tender abdomen, seek immediate medical attention as these could be symptoms of pancreatitis.

Key Considerations

• The mechanism behind this association likely involves GLP-1 receptors in the pancreas, which when stimulated may increase pancreatic enzyme production or alter pancreatic duct pressure in susceptible individuals 1.
• Healthcare providers typically weigh this small risk against the significant benefits of semaglutide for diabetes management or weight loss, as indicated in the 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes 1.
• Most patients tolerate the medication well without developing pancreatitis, and the overall risk-benefit profile remains favorable for appropriate candidates.

Important Warnings and Precautions

• Patients with a history of serious hypersensitivity reaction to the drug, severe renal impairment, or end-stage renal disease should use semaglutide with caution or under close medical supervision 1.
• Semaglutide has also been associated with diabetic retinopathy complications, which may be related to its associated rapid and marked glucose and A1C reductions 1.

Monitoring and Management

• Patients taking semaglutide should be monitored for signs and symptoms of pancreatitis, and the medication should be discontinued if pancreatitis is suspected and not restarted if pancreatitis is confirmed 1.
• The dose of semaglutide should be up-titrated slowly to reduce nausea and vomiting, and patients with prior gastric surgery should be treated with caution 1.

From the FDA Drug Label

Acute Pancreatitis: Has been observed in patients treated with GLP-1 receptor agonists, including WEGOVY. Discontinue promptly if pancreatitis is suspected. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists, including WEGOVY [see Adverse Reactions (6)] The following adverse reactions have been reported during post-approval use of semaglutide, the active ingredient of WEGOVY. ... Gastrointestinal Disorders: acute pancreatitis and necrotizing pancreatitis, sometimes resulting in death;

Semaglutide may cause pancreatitis. The drug label warns of the risk of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients treated with GLP-1 receptor agonists, including semaglutide. If pancreatitis is suspected, the drug should be discontinued promptly.

• Key points:
  • Acute pancreatitis has been observed in patients treated with semaglutide.
  • The risk of pancreatitis is a known adverse reaction associated with GLP-1 receptor agonists.
  • Patients should be monitored for signs and symptoms of acute pancreatitis.
  • Discontinue semaglutide if pancreatitis is suspected. 2, 2, 2

From the Research

Semaglutide and Pancreatitis

• Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has been associated with pancreatitis in some case reports 3, 4, 5.
• These case reports describe patients who developed acute pancreatitis after starting semaglutide, with some cases being severe and even fatal 3.
• However, a larger study found that the use of GLP-1 receptor agonists, including semaglutide, was not associated with an increased risk of pancreatitis in a comorbidity-free subgroup of patients with type 2 diabetes 6.
• Another study reviewed the safety of semaglutide and found that it induces mostly mild-to-moderate and transient gastrointestinal disturbances, but does not increase the risk of pancreatic cancer or pancreatitis 7.

Key Findings

• The evidence suggests that while there have been cases of pancreatitis associated with semaglutide use, the overall risk of pancreatitis may not be increased with GLP-1 receptor agonist use 6.
• Clinicians should be aware of the potential for semaglutide to cause acute pancreatitis, especially in patients with a history of pancreatic disease or other risk factors 4, 5.
• Further research is needed to fully understand the relationship between semaglutide and pancreatitis, and to determine the underlying mechanisms of this potential association 3, 7.