Dipeptidyl peptidase IV inhibitors

General information

Sitagliptin ([2R]-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro(1,2,4)triazolo(4,3-a)pyrazin-7(8H)-yl]-1-[2,4,5-trifluorophenyl]butan-2-amine) [ ] was the first inhibitor of dipeptidyl peptidase type 4 (DPP-4) to have received a licence in the UK (in 2007). Other are linagliptin, saxagliptin, and vildagliptin.

DPP-4 is an enzyme that is involved in the rapid metabolism of incretins, such as glucagon-like peptide. Inhibitors of DPP-4 therefore extend the action of incretins. The incretins increase glucose-dependent insulin secretion from the pancreas, and so inhibition of DPP-4 is a therapeutic approach in the treatment of type 2 diabetes. Unlike the incretin mimetic analogues of glucagon-like peptide, which are given subcutaneously, inhibitors of DPP-4 can be given orally.

There are other closely related DPP enzymes, such as DPP-8 and DPP-9. When these enzymes are inhibited in experimental animals multiorgan toxicity occurs.