Pancreatic Adverse Effect of Glucagon-Like Peptide-1 Receptor Agonist Based on cis Mendelian Randomization and US FAERS Database

doi:10.19803/j.1672-8629.20250284

Abstract

Abstract: Objective To investigate the causal relationship between GLP-1RA medications and pancreatic-related adverse event (AE) using Mendelian randomization (MR) before mining AE signals for causal AE using the FDA Adverse Event Reporting System (FAERS) database from 1 Jan, 2018 to 30 Sep, 2024. Methods The inverse variance weighting method was used as the primary analysis method for MR. Chi-square test and three disproportionality analysis methods were combined to mine AE signals. Results GLP-1RA medications were found to have causal associations with acute pancreatitis (OR=1.003, 95%CI:1.002–1.004, P＜0.000 1) and chronic pancreatitis (OR=1.434, 95%CI:1.231–1.670, P＜0.000 1). No causal associations were found with pancreatic cancer (ORBI-DDBJ=1.444, 95%CI:0.818–1.222, P=2.549; ORMRC-IEU=0.856, 95%CI: 0.294–2.497, P=0.776 5). In the FAERS database, 11 261 704 AE reports were obtained from five clinically commonly used GLP-1RA medications, and 10 types of AE signals related to pancreatitis were identified. Stratified analysis revealed that AE signals primarily involved groups ages 45 to 64 and ages 65 and older, with similar types of AE across these age groups. For dulaglutide, exenatide and liraglutide, the types of signal AE were the same in both male and female stratum. Conclusion GLP-1RA medications can increase the risk of pancreatitis rather than pancreatic cancer. Signal mining of the FAERS data reveals the characteristics of pancreatitis-related AE associated with different GLP-1RA medications.

Key words: Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA), Mendelian Randomization, FDA Adverse Event Reporting System (FAERS), Adverse Drug Reaction, Data Mining, Pancreatitis

CLC Number:

R977
R994.11

LI Yue, GUO Xiaojing, WU Bo, PAN Tingting, WANG Yanqing, TAO Wenhui. Pancreatic Adverse Effect of Glucagon-Like Peptide-1 Receptor Agonist Based on cis Mendelian Randomization and US FAERS Database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(12): 1418-1423.

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URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20250284

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I12/1418

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