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Glucagon-like peptide 1 receptor agonists and the potential risk of pancreatic carcinoma: a pharmacovigilance study using the FDA Adverse Event Reporting System and literature visualization analysis

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International Journal of Clinical Pharmacy Aims and scope Submit manuscript

Abstract

Background

There are increasing data on the potential risk of pancreatic carcinoma associated with glucagon-like peptide 1 receptor agonists (GLP-1RAs).

Aim

The study aimed to determine whether GLP-1RAs are associated with increased detection of pancreatic carcinoma based on the FDA Adverse Events Reporting System and clarify its potential mechanisms through keyword co-occurrence analysis from literature database.

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. VOSviewer was adopted to generate visual analysis of keyword hotspots.

Results

A total of 3073 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 (63.6%). Based on the bibliometric investigation, cAMP/protein-kinase, Ca2+ channel, endoplasmic-reticulum stress, and oxidative stress are potential pathogenesis of pancreatic carcinoma resulting from GLP-1RAs.

Conclusion

Based on this pharmacovigilance study, GLP-1RAs, except albiglutide, are associated with pancreatic carcinoma.

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Acknowledgements

None.

Funding

This study was supported by the Chinese Society of Toxicology Clinical Toxicology Project (number CST2020CT109) and the Beijing Hospital Authority Youth Programme (number QML20180503).

Author information

Author notes

  1. Bin Zhu and Zhigang Zhao contributed equally to this work.

  2. Mingnan Cao and Chen Pan contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China

    Mingnan Cao, Yue Tian, Zhigang Zhao & Bin Zhu

  2. Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China

    Chen Pan

  3. Department of Pharmacy, Peking University International Hospital, Beijing, 102206, China

    Li Wang

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  1. Mingnan Cao
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Correspondence to Bin Zhu.

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Cao, M., Pan, C., Tian, Y. et al. Glucagon-like peptide 1 receptor agonists and the potential risk of pancreatic carcinoma: a pharmacovigilance study using the FDA Adverse Event Reporting System and literature visualization analysis. Int J Clin Pharm 45, 689–697 (2023). https://doi.org/10.1007/s11096-023-01556-2

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