title: GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus.
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.
authors.affiliation: Division of Diabetology, St Josef-Hospital, Ruhr-University Bochum, Gudrunstraße 56, 44791 Bochum, Germany. juris.meier@rub.de
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069450:Liraglutide; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use; D057285:Precision Medicine / Q000379:methods*; D017433:Protein Structure, Secondary; D016896:Treatment Outcome; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide