Pharmacogenetics of Type 2 Diabetes-Progress and Prospects

Int J Mol Sci. 2020 Sep 18;21(18):6842. doi: 10.3390/ijms21186842.

Abstract

Type 2 diabetes mellitus (T2D) is a chronic metabolic disease resulting from insulin resistance and progressively reduced insulin secretion, which leads to impaired glucose utilization, dyslipidemia and hyperinsulinemia and progressive pancreatic beta cell dysfunction. The incidence of type 2 diabetes mellitus is increasing worldwide and nowadays T2D already became a global epidemic. The well-known interindividual variability of T2D drug actions such as biguanides, sulfonylureas/meglitinides, DPP-4 inhibitors/GLP1R agonists and SGLT-2 inhibitors may be caused, among other things, by genetic factors. Pharmacogenetic findings may aid in identifying new drug targets and obtaining in-depth knowledge of the causes of disease and its physiological processes, thereby, providing an opportunity to elaborate an algorithm for tailor or precision treatment. The aim of this article is to summarize recent progress and discoveries for T2D pharmacogenetics and to discuss the factors which limit the furthering accumulation of genetic variability knowledge in patient response to therapy that will allow improvement the personalized treatment of T2D.

Keywords: DPP-4 inhibitors; GLP1R agonists; SGLT-2 inhibitors; meglitinides; metformin; pharmacogenetics; polymorphism; sulfonylureas; type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Benzamides / therapeutic use*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin / therapeutic use*
  • Pharmacogenetics*
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Sulfonylurea Compounds / therapeutic use*

Substances

  • Benzamides
  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Sulfonylurea Compounds
  • meglitinide
  • Metformin