Do incretin-based therapies cause acute pancreatitis?

Area of Science:

• Endocrinology
• Pharmacovigilance
• Gastroenterology

Background:

• Postmarketing surveillance identified pancreatitis reports associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs).
• Initial concerns arose with exenatide (Byetta), leading to package insert updates.
• Similar reports have emerged for sitagliptin (Januvia/Janumet).

Purpose of the Study:

• To investigate the potential causal relationship between GLP-1 RAs and acute pancreatitis.
• To evaluate whether the observed pancreatitis cases represent a true drug-induced risk or are incidental findings in the treated population.

Main Methods:

• Review of postmarketing safety reports submitted to the Food and Drug Administration (FDA).
• Analysis of pancreatitis cases, including hemorrhagic or necrotizing pancreatitis, linked to exenatide and sitagliptin use.
• Examination of package insert revisions for these medications.

Main Results:

• Six reports of hemorrhagic pancreatitis, with two fatalities, were linked to exenatide.
• To date, 88 cases of acute pancreatitis, including two hemorrhagic/necrotizing cases, have been reported for sitagliptin.
• Package inserts for both medications have been revised due to these safety concerns.

Conclusions:

• The increasing number of pancreatitis reports necessitates further investigation into the association with GLP-1 RAs.
• Determining causality versus incidental findings is crucial for patient safety and clinical practice.
• Ongoing data examination is required to clarify the risk profile of these widely used diabetes medications.