Peptide degradation and the role of DPP-4 inhibitors in the treatment of type 2 diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

57 Citations (Scopus)

Abstract

Dipeptidyl peptidase-4 (DPP-4) inhibitors are now a widely used, safe and efficacious class of antidiabetic drugs, which were developed prospectively using a rational drug design approach based on a thorough understanding of the endocrinology and degradation of glucagon-like peptide-1 (GLP-1). GLP-1 is an intestinal hormone with potent insulinotropic and glucagonostatic effects and can normalise blood glucose levels in patients with type 2 diabetes, but the native peptide is not therapeutically useful because of its inherent metabolic instability. Using the GLP-1/DPP-4 system and type 2 diabetes as an example, this review summarises how knowledge of a peptide's biological effects coupled with an understanding of the pathways involved in its metabolic clearance can be exploited in a rational, step-by-step manner to develop a therapeutic agent, which is effective and well tolerated, and any side effects are minor and largely predictable. Other peptides with metabolic effects which can also be degraded by DPP-4 will be reviewed, and their potential role as additional mediators of the effects of DPP-4 inhibitors will be assessed.

Original languageEnglish
JournalPeptides
Volume100
Pages (from-to)150-157
Number of pages8
ISSN0196-9781
DOIs
Publication statusPublished - Feb 2018

Keywords

  • Dipeptidyl peptidase.4
  • Glucagon-like peptide-1
  • Incretin
  • Peptide degradation
  • Therapy
  • Type 2 diabetes

Cite this