A review on the association between glucagon-like peptide-1 receptor agonists and thyroid cancer.
There is a concern on the risk of thyroid cancer associated with glucagon-like peptide-1 (GLP-1) analogs including liraglutide and exenatide. In this article, we review related experimental studies, clinical trials and observational human studies currently available. In rodents, liraglutide activated the GLP-1 receptors on C-cells, causing an increased incidence of C-cell neoplasia. Animal experiments with monkeys demonstrated no increase in calcitonin release and no C-cell proliferation after long-term liraglutide administration. Longitudinal 2-year data from clinical trials do not support any significant risk for the activation or growth of C-cell cancer in humans in response to liraglutide. However, an analysis of the FDA adverse event reporting system database suggested an increased risk for thyroid cancer associated with exenatide after its marketing. Noticeably, a recent study discovered that GLP-1 receptor could also be expressed in human papillary thyroid carcinomas (PTC), but the impact of GLP-1 analogs on PTC is not known. Therefore, GLP-1 analogs might increase the risk of thyroid C-cell pathology in rodents, but its risk in humans awaits confirmation. Since GLP-1 receptor is also expressed in PTC besides C-cells, it is important to investigate the actions of GLP-1 on different subtypes of thyroid cancer in the future.
Department of Internal Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
Wei-Yih
WY
Chiu
Shyang-Rong
SR
Shih
Chin-Hsiao
CH
Tseng
D000818:Animals; D002986:Clinical Trials as Topic; D048909:Diabetes Complications / Q000175:diagnosis; D003920:Diabetes Mellitus / Q000188:drug therapy; D004195:Disease Models, Animal; D000077270:Exenatide; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000494:pharmacology; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D000069450:Liraglutide; D008252:Macaca fascicularis; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D018027:Receptors, Glucagon / Q000819:agonists*; D013964:Thyroid Neoplasms / Q000150:complications / Q000209:etiology / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology*
C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide