4.7 Article

Pharmacogenomics of GLP-1 receptor agonists: Focus on pharmacological profile

Journal

EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 936, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.ejphar.2022.175356

Keywords

Pharmacogenomics; GLP-1RAs; Pharmacodynamics; Pharmacokinetics; Oral-antidiabetic drugs

Funding

  1. DST-FIST [SR/FST/LS-I/2017/49]

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This review discusses the role and influencing factors of GLP-1RA drugs in the treatment of type 2 diabetes, as well as information on their pharmacokinetics and pharmacodynamics.
Type 2 Diabetes mellitus (T2DM) is a multifactorial metabolic disorder also known as a silent killer disease. Macrovascular and microvascular complications associated with diabetes worsen the condition leading to higher comorbidity and mortality rate. Currently, available treatment strategies for diabetes include biguanides, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, insulin and its analogs, DPP-4 (dipeptidyl-peptidase4) inhibitors, SGLT-2 inhibitors, and Glucagon Like Peptide-1 receptor agonists (GLP-1RAs). Synthetic agonists of GLP-1 hormone, GLP-1RAs are an emerging class of anti-diabetic drugs which target the pathophysiology of diabetes through various mechanisms and at multiple sites. They promote insulin secretion from beta cells, and the proliferation of beta cells inhibits glucagon secretion, delays gastric emptying and induces satiety. However, treatment is reported to be associated with inter-individual variations and adverse drug reactions, which are also influenced by genetic variations. There have been a few pharmacogenetic studies have been carried out on this drug class. This review discusses all the available GLP-1RAs, their pharmacokinetics, pharmacodynamics and genetic variation affecting the inter-individual variation.

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