Glucagon-like peptide 1 receptor agonists and the potential risk of pancreatic carcinoma: a real-world pharmacovigilance study of post-marketing surveillance data

Author:

Cao Mingnan1,Pan Chen2,Tian Yue1,Wang Li3,Zhao Zhigang1ORCID,Zhu Bin1

Affiliation:

1. Beijing Tiantan Hospital

2. Capital Medical University Affiliated Beijing Friendship Hospital

3. Peking University International Hospital

Abstract

Abstract Background There are conflicting data on the potential risks of pancreatic carcinoma associated with glucagon-like peptide 1 receptor agonists (GLP-1RAs). Aim The study aimed to determine whether GLP-1RAs were associated with increased detection of pancreatic carcinoma based on the FDA Adverse Events Reporting System (FAERS) and clarify its potential mechanisms through keyword co-occurrence analysis. Method Disproportionality and Bayesian analyses were used for signal detection using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Mortality, life-threatening events, and hospitalizations were also investigated. Keyword co-occurrence analysis of publications was adopted to uncover potential molecular mechanisms. Results A total of 3,073 pancreatic carcinoma cases were related to GLP-1RAs. Five GLP-1RAs were detected with signals for pancreatic carcinoma. Liraglutide had the strongest signal detection (ROR 54.45, 95% CI 51.21-57.90; PRR 52.52, 95%CI 49.49-55.73; IC 5.59; EBGM 48.30). The signals of exenatide (ROR 37.32, 95%CI 35.47-39.28; PRR 36.45, 95%CI 34.67-38.32; IC 5.00; EBGM 32.10) and lixisenatide (ROR 37.07, 95%CI 9.09-151.09; PRR 36.09; 95%CI 9.20-141.64; IC 5.17, EBGM 36.09) were stronger than those of semaglutide (ROR 7.43, 95%CI 5.22-10.57; PRR 7.39; 95%CI 5.20-10.50; IC 2.88, EBGM 7.38) and dulaglutide (ROR 6.47, 95%CI 5.56-7.54; PRR 6.45; 95%CI 5.54-7.51; IC 2.67, EBGM 6.38). The highest mortality rate occurred in exenatide (63.58%). cAMP/protein-kinase, Ca2+ channel, endoplasmic-reticulum stress, and oxidative stress are potential pathogenesis of pancreatic carcinoma resulted from GLP-1RAs. Conclusion GLP-1RAs, except albiglutide, are associatedwith pancreatic carcinoma based on the pharmacovigilance study.

Publisher

Research Square Platform LLC

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