Genetic variations in GLP-1R: Impact on diabetes and obesity therapeutics

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that is essential for glucose homeostasis, energy balance and appetite. GLP-1R is a key therapeutic target for the treatment of type 2 diabetes and obesity, owing to its central role in insulin secretion, glucagon suppression, and body weight regulation. Increasing evidence suggests that genetic polymorphisms in GLP-1R can influence the expression of the receptor, ligand binding, and downstream signalling processes, thereby affecting individual responses to GLP-1R agonists. Understanding these variants is essential for advancing precision medicine, as inter-individual genetic differences can influence both therapeutic efficacy and susceptibility to adverse events. This review highlights the current knowledge on GLP-1R polymorphisms, with particular focus on their structural and functional consequences and their potential clinical implications.