The new insights from DPP-4 inhibitors: their potential immune modulatory function in autoimmune diabetes

Diabetes Metab Res Rev. 2014 Nov;30(8):646-53. doi: 10.1002/dmrr.2530.


Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control and protect β-cell function in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein CD26 and plays an important role in T-cell immunity. Autoimmune diabetes, a T-cell mediated organ-specific disease, is initiated by the imbalance between pathogenic and regulatory T-lymphocytes. DPP-4 inhibitors can suppress pathogenic effects of Th1 and Th17 cells and up-regulate Th2 cells and regulatory T cells, which play a critical role in ameliorating autoimmune diabetes. This provides a basis for the potential use of DPP-4 inhibitors in the treatment of autoimmune diabetes. Recent studies suggest that DPP-4 inhibitors improve β-cell function and attenuate autoimmunity in type 1 diabetic mouse models. However, there are few clinical studies on the treatment of autoimmune diabetes with DPP-4 inhibitors. Further studies are warranted to confirm the therapeutic effects of DPP-4 inhibitors on autoimmune diabetes in humans.

Keywords: DPP-4 inhibitors; T cell; TGF-β; Treg; autoimmune diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmunity / drug effects*
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / metabolism
  • Dipeptidyl Peptidase 4 / chemistry
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Humans
  • Immunologic Factors / therapeutic use*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / immunology
  • Insulin-Secreting Cells / metabolism
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism


  • Dipeptidyl-Peptidase IV Inhibitors
  • Immunologic Factors
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4