Does zepbound (tirzepatide) cause pancreatitis?

Does Zepbound Cause Pancreatitis?

Acute pancreatitis has been reported with tirzepatide (Zepbound), but a causal relationship has not been definitively established. The risk appears to be similar to other GLP-1 receptor agonists, with rare occurrences that warrant monitoring but should not prevent use in appropriate patients without pre-existing risk factors.

Risk Assessment and Evidence

• Tirzepatide (Zepbound), as a dual GIP and GLP-1 receptor agonist, carries a potential risk for pancreatitis similar to other medications in the GLP-1 receptor agonist class 1
• The FDA label for Zepbound specifically lists acute pancreatitis as a potential adverse reaction, instructing patients to discontinue the medication promptly and contact their healthcare provider if pancreatitis is suspected 2
• Recent meta-analyses of randomized controlled trials have found that tirzepatide has identical risks of pancreatitis compared to placebo across all doses (5mg, 10mg, and 15mg), suggesting the absolute risk is low 3
• While tirzepatide can cause elevations in pancreatic enzymes (amylase and lipase) compared to placebo and insulin, these elevations do not necessarily translate to clinical pancreatitis 3

Clinical Presentation and Monitoring

• Patients should be monitored for symptoms of acute pancreatitis, which include:

  • Severe abdominal pain that may radiate to the back
  • Nausea and vomiting
  • Elevated pancreatic enzymes (amylase and lipase) 2

• Recent case reports have documented rare but serious cases of pancreatitis associated with tirzepatide use:

  • A case of fatal, fulminant, necrotizing pancreatitis in a 64-year-old female patient with recent tirzepatide initiation 4
  • A probable case in a 32-year-old woman who developed acute pancreatitis after five weeks of tirzepatide use 5

Risk Factors and Precautions

• The 2025 American Diabetes Association Standards of Care recommends:

  • Not initiating GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists in patients at high risk for pancreatitis 1
  • Discontinuing these medications if pancreatitis is suspected 1

• Patients with a history of pancreatitis, gallbladder disease, or excessive alcohol use may be at higher risk and should be monitored more closely 1

Clinical Recommendations

• Before initiating Zepbound:

  • Assess for history of pancreatitis or gallbladder disease 1
  • Consider baseline pancreatic enzyme levels in high-risk patients 3

• During treatment with Zepbound:

  • Educate patients about symptoms of pancreatitis and when to seek medical attention 2
  • Routine monitoring of pancreatic enzymes in asymptomatic patients is not recommended 1
  • If pancreatitis is suspected, discontinue Zepbound immediately and perform appropriate diagnostic evaluation 2

• If pancreatitis occurs:

  • Permanently discontinue Zepbound 2
  • Treat pancreatitis according to standard protocols 1
  • Consider alternative weight loss or diabetes management strategies 1

Conclusion

While there is a documented association between tirzepatide (Zepbound) and acute pancreatitis, the absolute risk appears to be low based on clinical trial data. The risk-benefit profile remains favorable for most patients without pre-existing pancreatic disease. However, clinicians should maintain vigilance, particularly when initiating therapy, and promptly evaluate any symptoms suggestive of pancreatitis.