GLP-1 based therapy for type 2 diabetes

Eur J Pharm Sci. 2006 May;28(1-2):96-108. doi: 10.1016/j.ejps.2006.01.003. Epub 2006 Feb 20.


Type 2 diabetes mellitus is a major and growing health problem throughout the world. Current treatment approaches include diet, exercise, and a variety of pharmacological agents including insulin, biguanides, sulfonylureas and thiazolidinediones. New therapies are still needed to control metabolic abnormalities, and also to preserve beta-cell mass and to prevent loss of beta-cell function. Glucagon-like peptide 1 (GLP-1) is a drug candidate which potentially fulfils these conditions. GLP-1 is an incretin hormone secreted by intestinal L-cells in response to meal ingestion is a novel pharmacological target with multiple antihyperglycemic actions. GLP-1 glucoregulatory actions include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. GLP-1 is rapidly inactivated by amino peptidase, dipeptidyl peptidase IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential therapy for type 2 diabetes. However, both the strategies are having their own advantages and limitations. The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 mimetics and DPP-IV inhibitors. Further, the potential advantages and the limitations of both the strategies are discussed.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus / drug therapy*
  • Diabetes Mellitus / physiopathology*
  • Dipeptidyl Peptidase 4 / metabolism
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / metabolism
  • Glucagon-Like Peptide 1 / physiology*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use
  • Receptors, Glucagon / agonists


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Protease Inhibitors
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Dipeptidyl Peptidase 4