The potential for renoprotection with incretin-based drugs

Tetsuhiro Tanaka, Yoshiki Higashijima, Takehiko Wada, Masaomi Nangaku

Research output: Contribution to journalReview articlepeer-review

88 Citations (Scopus)


Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions beyond glycemic control. Indeed, recent studies highlight the potential beneficial effects of incretin-based therapy in diabetic kidney disease (DKD). Experimental studies using various diabetic models suggest that incretins protect the vascular endothelium from injury by binding to GLP-1 receptors, thereby ameliorating oxidative stress and the local inflammatory response, which reduces albuminuria and inhibits glomerular sclerosis. In addition, there is some evidence that GLP-1 receptor agonists and DPP-4 inhibitors mediate sodium excretion and diuresis to lower blood pressure. The pleiotropic actions of DPP-4 inhibitors are ascribed primarily to their effects on GLP-1 signaling, but other substrates of DPP-4, such as brain natriuretic peptide and stromal-derived factor-1α, may have roles. In this review, we summarize recent studies of the roles of incretin-based therapy in ameliorating DKD and its complications.

Original languageEnglish
Pages (from-to)701-711
Number of pages11
JournalKidney international
Issue number4
Publication statusPublished - 2014 Jan 1


  • DPP-4
  • GLP-1
  • diabetes
  • diabetic nephropathy
  • incretin

ASJC Scopus subject areas

  • Nephrology


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