Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors

Expert Opin Emerg Drugs. 2004 May;9(1):155-66. doi: 10.1517/eoed.9.1.155.32952.

Abstract

Glucagon-like peptide-1 (GLP-1) is a peptide hormone from the gut that stimulates insulin secretion and protects beta-cells, inhibits glucagon secretion and gastric emptying, and reduces appetite and food intake. In agreement with these actions, it has been shown to be highly effective in the treatment of Type 2 diabetes, causing marked improvements in glycaemic profile, insulin sensitivity and beta-cell performance, as well as weight reduction. The hormone is metabolised rapidly by the enzyme dipeptidyl peptidase IV (DPP-IV) and, therefore, cannot be easily used clinically. Instead, resistant analogues of the hormone (or agonists of the GLP-1 receptor) are in development, along with DPP-IV inhibitors, which have been demonstrated to protect the endogenous hormone and enhance its activity. Agonists include both albumin-bound analogues of GLP-1 and exendin-4, a lizard peptide. Clinical studies with exendin have been carried out for > 6 months and have indicated efficacy in patients inadequately treated with oral antidiabetic agents. Orally active DPP-IV inhibitors, suitable for once-daily administration, have demonstrated similar efficacy. Diabetes therapy, based on GLP-1 receptor activation, therefore, appears very promising.

Publication types

  • Review

MeSH terms

  • Adenosine Deaminase / physiology
  • Adenosine Deaminase Inhibitors*
  • Afferent Pathways / physiology
  • Animals
  • Appetite / drug effects
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Dipeptidyl Peptidase 4 / physiology
  • Drug Therapy, Combination
  • Exenatide
  • Glucagon / agonists
  • Glucagon / analogs & derivatives*
  • Glucagon / metabolism
  • Glucagon / pharmacology
  • Glucagon / physiology*
  • Glucagon / therapeutic use
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / physiology
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Hypothalamus / drug effects
  • Hypothalamus / physiopathology
  • Insulin / biosynthesis
  • Insulin / genetics
  • Insulin / metabolism
  • Insulin Secretion
  • Intestinal Mucosa / innervation
  • Intestinal Mucosa / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism
  • Liraglutide
  • Lizards
  • Maleimides / therapeutic use
  • Mice
  • Mice, Knockout
  • Mice, Obese
  • Peptide Fragments / agonists
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Peptides / pharmacology
  • Peptides / therapeutic use
  • Proglucagon
  • Protein Precursors / agonists
  • Protein Precursors / metabolism
  • Protein Precursors / pharmacology
  • Protein Precursors / physiology*
  • Rats
  • Rats, Zucker
  • Receptors, Glucagon / agonists*
  • Receptors, Glucagon / deficiency
  • Receptors, Glucagon / physiology
  • Venoms / pharmacology
  • Venoms / therapeutic use

Substances

  • Adenosine Deaminase Inhibitors
  • CJC 1131
  • GLP1R protein, human
  • Glp1r protein, mouse
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Glycoproteins
  • Hypoglycemic Agents
  • Insulin
  • Maleimides
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Receptors, Glucagon
  • Venoms
  • Proglucagon
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Adenosine Deaminase