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Curr Clin Pharmacol. 2017;12(4):202-209. doi: 10.2174/1574884713666180221121512.

Pharmacogenetics of Glucagon-like Peptide-1 Agonists for the Treatment of Type 2 Diabetes Mellitus.

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Division of Endocrinology and Metabolism - Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece.
Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.



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.


Biomedical databases were searched to identify key articles in the field and their results are critically presented in this review.


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.


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.


Genetic studies; glucagon-like peptide-1 (GLP-1) agonists; incretins; pharmacogenetics; polymorphisms; type 2 diabetes mellitus

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