GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes

Horm Metab Res. Nov-Dec 2004;36(11-12):867-76. doi: 10.1055/s-2004-826178.


Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. It has therefore been explored as a novel treatment of type 2 diabetes. A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). Two strategies have been employed to overcome this obstacle as a treatment of diabetes. One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. These GLP-1 mimetics include exenatide and liraglutide. Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. Both these strategies have been successful in animal studies and in clinical studies of up to one year's treatment. This review will summarize the background and the current (mid 2004) clinical experience with these two strategies.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
  • Glucagon / blood
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Molecular Mimicry
  • Protease Inhibitors / pharmacology*
  • Protease Inhibitors / therapeutic use
  • Rats
  • Receptors, Glucagon / agonists*


  • Blood Glucose
  • GLP1R protein, human
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Protease Inhibitors
  • Receptors, Glucagon
  • Glucagon
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Dipeptidyl Peptidase 4