GLP-1 Receptor Agonists for Individualized Treatment of Type 2 Diabetes Mellitus

Nat Rev Endocrinol. 2012 Dec;8(12):728-42. doi: 10.1038/nrendo.2012.140. Epub 2012 Sep 4.

Abstract

In healthy humans, the incretin glucagon-like peptide 1 (GLP-1) is secreted after eating and lowers glucose concentrations by augmenting insulin secretion and suppressing glucagon release. Additional effects of GLP-1 include retardation of gastric emptying, suppression of appetite and, potentially, inhibition of β-cell apoptosis. Native GLP-1 is degraded within ~2-3 min in the circulation; various GLP-1 receptor agonists have, therefore, been developed to provide prolonged in vivo actions. These GLP-1 receptor agonists can be categorized as either short-acting compounds, which provide short-lived receptor activation (such as exenatide and lixisenatide) or as long-acting compounds (for example albiglutide, dulaglutide, exenatide long-acting release, and liraglutide), which activate the GLP-1 receptor continuously at their recommended dose. The pharmacokinetic differences between these drugs lead to important differences in their pharmacodynamic profiles. The short-acting GLP-1 receptor agonists primarily lower postprandial blood glucose levels through inhibition of gastric emptying, whereas the long-acting compounds have a stronger effect on fasting glucose levels, which is mediated predominantly through their insulinotropic and glucagonostatic actions. The adverse effect profiles of these compounds also differ. The individual properties of the various GLP-1 receptor agonists might enable incretin-based treatment of type 2 diabetes mellitus to be tailored to the needs of each patient.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism*
  • Exenatide
  • Glucagon-Like Peptide 1 / agonists*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide 1 / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide
  • Molecular Sequence Data
  • Peptides / pharmacology
  • Peptides / therapeutic use
  • Precision Medicine / methods*
  • Protein Structure, Secondary
  • Treatment Outcome
  • Venoms / pharmacology
  • Venoms / therapeutic use

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Peptides
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Exenatide