Is tirzepatide (a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist) safe to use in patients with a history of pancreatitis?

From the Guidelines

Tirzepatide is not recommended for patients with a history of pancreatitis due to the increased risk of developing pancreatitis again. This medication, like other GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists, carries a warning about pancreatitis as a potential serious adverse effect, as noted in the 2025 standards of care in diabetes 1. The risk is particularly concerning for those with a prior history of pancreatic inflammation. According to a recent narrative review of clinical pharmacology and implications for peri-operative practice, acute pancreatitis has been linked to the use of exenatide, a GLP-1 receptor agonist, in reports submitted to the US Food and Drug Administration Adverse event reporting system and in observational studies 1.

Key Considerations

• The mechanism behind this risk involves the medication's effects on pancreatic enzyme secretion and potential direct effects on pancreatic tissue.
• Current guidelines recommend using GLP-1 receptor agonists with caution if they are needed in patients with type 2 diabetes mellitus who have a history of pancreatitis 1.
• Instead of tirzepatide, alternative medications that don't carry this risk profile should be discussed with a healthcare provider.
• Other weight management or diabetes treatment options such as metformin, SGLT-2 inhibitors, or other classes of medications that don't have the same pancreatic risk profile may be considered.

Important Warnings

• Patients with a history of pancreatitis should avoid using tirzepatide due to the increased risk of developing pancreatitis again.
• It is essential to disclose complete medical history, especially previous pancreatitis, to a healthcare provider when discussing medication options.
• The use of GLP-1 receptor agonists, including tirzepatide, should be approached with caution in patients with a history of pancreatitis, and alternative treatment options should be explored to minimize the risk of adverse effects.

From the FDA Drug Label

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 Limitations of Use: Has not been studied in patients with a history of pancreatitis (1,5.2)

The use of tirzepatide in patients with a history of pancreatitis is not recommended due to the lack of studies and unknown risk. If pancreatitis is suspected, discontinue tirzepatide and initiate appropriate management 2, 2, 2.

From the Research

Safety of Tirzepatide in Patients with a History of Pancreatitis

• The safety of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, in patients with a history of pancreatitis has been evaluated in several studies 3, 4, 5, 6.
• A retrospective cohort study found that tirzepatide users had a lower recurrence rate of acute pancreatitis (6.2%) compared to semaglutide users (11.7%) and non-users (40.9%) 3.
• A narrative review suggested that the use of tirzepatide is not significantly associated with an increased risk of acute pancreatitis, although more studies are needed to confirm its safety 4.
• A case report described a patient who developed acute pancreatitis after switching from semaglutide to tirzepatide, highlighting the need for clinical awareness and careful dose adjustments when transitioning between GLP-1 agonists 5.
• A systematic review and meta-analysis found that tirzepatide had identical risks of pancreatitis to placebo and was associated with comparable risks of pancreatitis to insulin and GLP-1RAs 6.

Pancreatic Safety and Islet Cell Function

• The meta-analysis also found that tirzepatide caused greater increases in pancreatic amylase and lipase than placebo and insulin, although the clinical significance of this is unclear 6.
• Tirzepatide was associated with greater percent reductions in fasting insulin, C-peptide, and glucagon than GLP-1RAs, and greater percent reductions in HOMA2-IR than placebo and GLP-1RAs 6.
• A systematic review of acute pancreatitis as an adverse event of type 2 diabetes drugs found that the question of whether antidiabetes drugs can cause acute pancreatitis is complex and requires a balanced position 7.