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

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

Volume: 12 Issue: 4

Author(s): Spyridon N. Karras, Eleni Rapti, Theocharis Koufakis, Angeliki Kyriazou, Dimitrios G. Goulis and Kalliopi Kotsa*

Affiliation:

• Division of Endocrinology and Metabolism - Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki,Greece

Keywords: Genetic studies, glucagon-like peptide-1 (GLP-1) agonists, incretins, pharmacogenetics, polymorphisms, type 2 diabetes mellitus.

Abstract: 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.

Cite this article as:

Karras N. Spyridon , Rapti Eleni , Koufakis Theocharis , Kyriazou Angeliki , Goulis G. Dimitrios and Kotsa Kalliopi *, Pharmacogenetics of Glucagon-like Peptide-1 Agonists for the Treatment of Type 2 Diabetes Mellitus, Current Clinical Pharmacology 2017; 12 (4) . https://dx.doi.org/10.2174/1574884713666180221121512