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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.

Author information

1
Division of Endocrinology and Metabolism - Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece.
2
Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.

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.

KEYWORDS:

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

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