Incretin-based therapies: mimetics versus protease inhibitors

Trends Endocrinol Metab. 2007 Aug;18(6):240-5. doi: 10.1016/j.tem.2007.06.005. Epub 2007 Jul 12.


The physiological incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), lower blood glucose levels through multiple mechanisms, including enhancement of glucose-stimulated insulin secretion. Although of demonstrated benefit to glycemic control in patients with type 2 diabetes, particularly for GLP-1, the half-lives of these peptides are too short for practical therapeutic utility. Here, we discuss recent approaches to incretin-based therapy, including the use of long-acting GLP-1 receptor agonists, degradation-resistant GLP-1 analogs, GLP-1 analogs conjugated to albumin, non-peptide small molecules that bind to the GLP-1 receptor, and inhibitors of dipeptidyl peptidase IV, the enzyme that degrades both GIP and GLP-1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biomimetics*
  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors
  • Drug Design
  • Gastric Inhibitory Polypeptide / physiology*
  • Glucagon-Like Peptide 1 / physiology*
  • Humans
  • Hyperglycemia / drug therapy*
  • Hypoglycemic Agents / therapeutic use
  • Models, Biological
  • Molecular Sequence Data
  • Protease Inhibitors / therapeutic use*
  • Sequence Homology, Amino Acid


  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Protease Inhibitors
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1