BACKGROUND: Pharmacogenetics is a promising area of medical research, providing methods to identify the appropriate pharmaceutical agent and dosing for each unique patient. Glucagon- like peptide-1 (GLP-1) agonists are a novel therapeutic choice used in the treatment of type 2 diabetes mellitus (T2DM), demonstrating efficacy regarding glycemic control and weight loss. Therapeutic response to GLP-1 agonist treatment is a complex biophenomenon, dependent on a plethora of modifiable (diet, exercise, adherence) and non-modifiable (genetic individual variants, ethnic characteristics) parameters. Ιn this context, it has been hypothesized that genetic polymorphisms of GLP-1 related genes may be associated with the therapeutic response to GLP-1 agonist treatment. This review focuses on the most important polymorphisms of the GLP-1 biological network that could affect clinical response to GLP-1 agonist treatment.METHODS: Biomedical databases were searched to identify key articles in the field and their results are critically presented in this review.RESULT: Recent pharmacological and clinical studies demonstrated a significant variation in GLP-1 agonist treatment, in cohorts with homogeneous adherence to diet, exercise and antidiabetic treatment. These studies identified several cases of non-responders to GLP-1 agonist therapy, in association with specific allelic patterns of GLP-1 receptor or other biomolecules implicated in glucose homeostasis.CONCLUSION: Although the exact DNA sequences that cause the molecular changes leading to a variable response to GLP-1 agonists have not been yet fully identified, these findings underline the importance of an individualized approach in anti-diabetic treatment.