Incretin mimetics as emerging treatments for type 2 diabetes

Ann Pharmacother. 2005 Jan;39(1):110-8. doi: 10.1345/aph.1E245. Epub 2004 Nov 23.


Objective: To review the physiology, pharmacology, and clinical efficacy of glucagon-like peptide (GLP-1) and the incretin mimetics exenatide and liraglutide in clinical studies.

Data sources: Primary literature obtained via MEDLINE (1966-April 2004) and International Pharmaceutical Abstracts (1970-April 2004) searches; abstracts obtained from meeting sources and manufacturers.

Study selection and data extraction: All English-language studies and abstracts evaluating GLP-1, exenatide, and liraglutide in the treatment of patients with type 2 diabetes were reviewed. Data from animal studies were also included if human data were not available. Primary and review articles related to the physiology, development, and evaluation of GLP-1s were reviewed.

Data synthesis: GLP-1, exenatide (exendin-4, AC2993), and liraglutide (NN2211) are incretin mimetics that have been shown in human studies to be an effective treatment to improve glycemic control in patients with type 2 diabetes. Mechanisms by which these compounds improve glycemic control include enhancing glucose-dependent pancreatic secretion of insulin in response to nutrient intake, inhibiting glucagon secretion, delaying gastric emptying, and promoting early satiety. GLP-1 has been shown to promote pancreatic progenitor cell differentiation and improve beta-cell function and lifespan. Reported adverse effects of exenatide and liraglutide include nausea, vomiting, and transient headache, as well as increased risk of hypoglycemia when used with sulfonylureas.

Conclusions: Clinical studies show that GLP-1, exenatide, and liraglutide improve glycemic control for patients with type 2 diabetes through unique mechanisms not available with current pharmaceutical products. Ongoing Phase III studies will help to further position these compounds as treatment options for patients with type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Exenatide
  • Glucagon / adverse effects
  • Glucagon / analogs & derivatives*
  • Glucagon / pharmacokinetics
  • Glucagon / physiology
  • Glucagon / therapeutic use*
  • Glucagon-Like Peptide 1
  • Humans
  • Hypoglycemic Agents / pharmacokinetics
  • Hypoglycemic Agents / therapeutic use*
  • Liraglutide
  • Peptide Fragments / adverse effects
  • Peptide Fragments / physiology
  • Peptide Fragments / therapeutic use*
  • Peptides / pharmacokinetics
  • Peptides / therapeutic use*
  • Protein Precursors / adverse effects
  • Protein Precursors / physiology
  • Protein Precursors / therapeutic use*
  • Venoms / pharmacokinetics
  • Venoms / therapeutic use*


  • Hypoglycemic Agents
  • Peptide Fragments
  • Peptides
  • Protein Precursors
  • Venoms
  • Liraglutide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Exenatide