Should we still be concerned about the potential side effects of glucagon-like peptide-1 receptor agonists on thyroid C cells?

In recent years, numerous novel anti-diabetic drugs have emerged. Among them, glucagon-like peptide-1 receptor (GLP-1R) agonists developed on the basis of the incretin theory are the most popular and surprising. Thus far, the clinical and experimental efficiency and safety data seem to be good. However, questions about the side effects of GLP-1R agonists, especially on thyroid C cells, still remain. In vivo and in vitro rodent experiments have shown the potential risks of GLP-1R agonists on thyroid C cells. However, the effects of GLP-1R agonists in humans, which have only been studied in experiments using untreated thyroid tissues or C-cell lines, are questionable and differ from that in rodents. C-cell abnormalities are not only dependent on GLP-1R, as many other factors also influence the structure and function of thyroid C cells. Furthermore, there is not enough information from patients with diabetes or tissue samples from subjects treated with GLP-1R agonists and related drugs--especially data obtained during the prandial period or from a long-term study. Therefore, it is important to focus on the possible side effects of GLP-1R agonists on thyroid C cells.