Role of GLP-1 and DPP-4 in diabetic nephropathy and cardiovascular disease

Clin Sci (Lond). 2013 Jan;124(1):17-26. doi: 10.1042/CS20120167.

Abstract

Although there have been major advances in the understanding of the molecular mechanisms that contribute to the development of diabetic nephropathy, current best practice still leaves a significant treatment gap. The incidence of diabetes and associated nephropathy is increasing, with the main cause of mortality being related to cardiovascular causes. Novel therapies which are both 'cardio-renal'-protective seem the logical way forward. In the present review, we discuss the GLP-1 (glucagon-like peptide-1) receptor agonists and DPP-4 (dipeptidyl peptidase-4) inhibitors (incretin-based therapies), which are novel antidiabetic agents used in clinical practice and their role in diabetic nephropathy with specific focus on renoprotection and surrogate markers of cardiovascular disease. We discuss the pleiotropic effects of the incretin-based therapies apart from glucose-lowering and highlight the non-GLP-1 effects of DPP (dipeptidyl peptidase) inhibition. Large-scale clinical studies with cardiovascular end points are underway; however, studies with renal end points are lacking but much needed.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism*
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor
  • Humans
  • Incretins / metabolism*
  • Incretins / therapeutic use
  • Receptors, Glucagon / agonists*

Substances

  • Biomarkers
  • Dipeptidyl-Peptidase IV Inhibitors
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Incretins
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4