Prescribing Mounjaro (Tirzepatide) in Patients with History of Pancreatitis
Mounjaro (tirzepatide) should not be prescribed to patients with a history of pancreatitis due to the risk of recurrent pancreatitis, as clearly stated in the FDA label. 1
Contraindication and Risk Assessment
The FDA label for Mounjaro (tirzepatide) specifically addresses this issue:
"MOUNJARO has not been studied in patients with a prior history of pancreatitis. It is unknown if patients with a history of pancreatitis are at higher risk for development of pancreatitis on MOUNJARO." 1
Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been observed in patients treated with GLP-1 receptor agonists. 1
In clinical studies, 14 events of acute pancreatitis were confirmed in 13 MOUNJARO-treated patients (0.23 patients per 100 years of exposure) versus 3 events in comparator-treated patients. 1
Evidence of Pancreatitis Risk with Tirzepatide
Recent evidence further supports this contraindication:
A 2024 case report documented acute pancreatitis in a patient who switched from semaglutide to tirzepatide, highlighting the risk even when transitioning between GLP-1 receptor agonists. 2
A 2025 case report described a fatal case of fulminant, necrotizing pancreatitis in a low-risk female patient who had recently initiated tirzepatide, suggesting that severe complications can occur even in patients without obvious risk factors. 3
The American Diabetes Association's 2025 Standards of Care in Diabetes notes that pancreatitis is a reported adverse effect of GLP-1 receptor agonists, including tirzepatide. 4
Alternative Treatment Options
For patients with a history of pancreatitis who need diabetes treatment, consider these alternatives:
Metformin: First-line therapy with minimal risk of pancreatitis. Monitor for vitamin B12 deficiency and adjust dosing based on eGFR. 4
SGLT2 inhibitors: Good option with cardiovascular and renal benefits, without pancreatitis risk. 4
DPP-4 inhibitors: While they have a mechanism related to GLP-1, they have a different risk profile. However, the ADA notes that pancreatitis has been reported with DPP-4 inhibitors, though causality hasn't been established. 4
Insulin: Can be used safely in patients with history of pancreatitis.
Monitoring and Management
If a patient with no history of pancreatitis is prescribed tirzepatide:
Monitor for signs and symptoms of pancreatitis (persistent severe abdominal pain, sometimes radiating to the back, with or without vomiting). 1
If pancreatitis is suspected, discontinue MOUNJARO immediately and initiate appropriate management. 1
Be aware that GLP-1 receptor agonists can cause changes in the pancreas that may lead to pancreatitis, and effects may persist even after discontinuation. 5
Conclusion
The risk of recurrent pancreatitis in patients with a history of this condition makes tirzepatide an inappropriate choice. While a meta-analysis showed that rates of acute pancreatitis were extremely low (≤1%) across all doses of tirzepatide 6, the FDA label clearly indicates that the medication has not been studied in patients with prior pancreatitis, and the potential for serious harm, including fatal pancreatitis, exists. Alternative glucose-lowering medications should be used in these patients.