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

Mar 28, 2023International journal of clinical pharmacy

Possible link between diabetes drugs that target GLP-1 receptors and pancreatic cancer risk based on FDA reports and research review

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Abstract

A total of 3073 pancreatic carcinoma cases were related to glucagon-like peptide 1 receptor agonists (GLP-1RAs).

Five GLP-1RAs showed signals for pancreatic carcinoma, with liraglutide having the strongest detection signal.
The reporting odds ratio for liraglutide was 54.45, indicating a significant association with pancreatic carcinoma.
Exenatide and lixisenatide also showed strong signals, with reporting odds ratios of 37.32 and 37.07, respectively.
Semaglutide and dulaglutide presented weaker signals with reporting odds ratios of 7.43 and 6.47, respectively.
The highest mortality rate associated with these medications was observed in exenatide at 63.6%.
Key potential mechanisms identified include cAMP/protein-kinase, calcium channel involvement, endoplasmic-reticulum stress, and oxidative stress.

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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, Cachannel, endoplasmic-reticulum stress, and oxidative stress are potential pathogenesis of pancreatic carcinoma resulting from GLP-1RAs. 2+

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

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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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