Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes

Regul Pept. 2004 Feb 15;117(2):77-88. doi: 10.1016/j.regpep.2003.10.028.


Exenatide (synthetic exendin-4), glucagon-like peptide-1 (GLP-1), and GLP-1 analogues have actions with the potential to significantly improve glycemic control in patients with diabetes. Evidence suggests that these agents use a combination of mechanisms which may include glucose-dependent stimulation of insulin secretion, suppression of glucagon secretion, enhancement of beta-cell mass, slowing of gastric emptying, inhibition of food intake, and modulation of glucose trafficking in peripheral tissues. The short in vivo half-life of GLP-1 has proven a significant barrier to continued clinical development, and the focus of current clinical studies has shifted to agents with longer and more potent in vivo activity. This review examines recent exendin-4 pharmacology in the context of several known mechanisms of action, and contrasts exendin-4 actions with those of GLP-1 and a GLP-1 analogue. One of the most provocative areas of recent research is the finding that exendin-4 enhances beta-cell mass, thereby impeding or even reversing disease progression. Therefore, a major focus of this is article an examination of the data supporting the concept that exendin-4 and GLP-1 may increase beta-cell mass via stimulation of beta-cell neogenesis, stimulation of beta-cell proliferation, and suppression of beta-cell apoptosis.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Division / drug effects
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Exenatide
  • Gastric Emptying
  • Glucagon / metabolism
  • Glucagon / therapeutic use
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin Secretion
  • Islets of Langerhans / physiology
  • Molecular Sequence Data
  • Nutritional Physiological Phenomena
  • Peptide Fragments / therapeutic use
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Protein Precursors / therapeutic use
  • Receptors, Glucagon / metabolism
  • Venoms / pharmacology*
  • Venoms / therapeutic use


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Receptors, Glucagon
  • Venoms
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide