Risks of Pancreatic Adverse Events Associated with Tirzepatide: a Disproportionality Analysis Using Spontaneous Adverse Event Reporting System Data

doi:10.19803/j.1672-8629.20241041

Abstract

Abstract: Objective To evaluate risks of pancreatic adverse events (AEs) caused by a newly marketed glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) receptor dual target agonist, tirzepatide, and to compare the pancreatic safety of tirzepatide with other previously marketed GLP-1 drugs. Methods Data from the FDA Adverse Event Reporting System (FAERS) was used for signal mining of AEs from first quarter of 2004 to third quarter of 2024 while the Japanese Adverse Drug Event Report Database (JADER) was searched for validation of signals from 2009 to 2023. All the data used in this study was released as of the third quarter of 2024. Disproportionality analysis was used to detect AE signals of tirzepatide and compare tirzepatide with other GLP-1RA drugs. Sensitivity analyses were conducted of indications and time-to-onset (TTO) to eliminate potential confounding caused by association between AE and indications, and insufficient AE accumulation time of tirzepatide. Results Tirzepatide showed significant risk signals for pancreatitis (ROR=7.80, 95%CI: 7.07-8.61) and pancreatic necrosis (ROR=3.76, 95%CI: 2.06-6.85). After the association between indications and AEs through sensitivity analysis was controlled, tirzepatide showed positive signals for pancreatitis (ROR=2.74, 95%CI: 2.16-3.47). Higher risks of pancreatitis were associated with semaglutide (ROR=2.04, 95%CI: 1.82-2.30), liraglutide (ROR=4.76, 95%CI: 4.34-5.22) and dulaglutide (ROR=2.01, 95%CI: 1.82-2.21). Conclusion sThe analysis of spontaneous AE reports suggests that tirzepatide can increase the risk of pancreatitis, but the chances are smaller compared with other GLP-1 receptor agonists. When tirzepatide is used clinically or GLP-1RA medications are opted for, clinicians ought to be alert to pancreatic adverse events.

Key words: Tirzepatide, Semaglutide, Glucagon-Like Peptide-1 Receptor Agonists, Type 2 Diabetes Mellitus, Pancreatitis, Adverse Drug Events, FAERS

CLC Number:

R977
R994.11

JING Tianshu, LU Guotao, WANG Shengfeng. Risks of Pancreatic Adverse Events Associated with Tirzepatide: a Disproportionality Analysis Using Spontaneous Adverse Event Reporting System Data[J]. Chinese Journal of Pharmacovigilance, 2025, 22(6): 669-673.

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https://zgywjj.magtechjournal.com/EN/Y2025/V22/I6/669

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