GCGR and Hyperglycemia: To reduce the risk of inducing hyperglycemia by GCGR signaling, GCGR agonism has been combined with other mechanisms, such as glucagon-like peptide-1 receptor (GLP-1R) agonism (17–19) and glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism (20), both of which stimulate insulin secretion upon the elevation of blood glucose.