Inhibition of dipeptidylpeptidase IV activity as a therapy of type 2 diabetes

Expert Opin Emerg Drugs. 2006 Sep;11(3):525-39. doi: 10.1517/14728214.11.3.525.


Dipeptidyl peptidase IV (DPP IV) is a ubiquitous, multifunctional, serine protease enzyme and receptor with roles in the control of endocrine and immune function, cell metabolism, growth and adhesion. As an enzyme, DPP IV cleaves the N-terminal dipeptide from the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. This inactivates the hormones, thereby cancelling their prandial insulinotropic effect. One approach to restore incretin activity as a therapy for Type 2 diabetes has been the development of DPP IV inhibitors. Inhibitors of DPP IV have shown efficacy and tolerability when used to control the hyperglycaemia of noninsulin-dependent animal models and human Type 2 diabetes. These DPP IV inhibitors prolong active incretin hormone concentrations and may exert additional antidiabetic effects. If long-term clinical trials confirm sustained and safe control of blood glucose, DPP IV inhibitors (known as 'gliptins') may be expected to provide a new treatment modality for Type 2 diabetes.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Molecular Sequence Data
  • Protease Inhibitors / pharmacology
  • Protease Inhibitors / therapeutic use*


  • Hypoglycemic Agents
  • Protease Inhibitors
  • Dipeptidyl Peptidase 4