Mechanism of action of inhibitors of dipeptidyl-peptidase-4 (DPP-4).
Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of the incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). The first available DPP-4 inhibitors are sitagliptin and vildagliptin. These compounds are orally active and have been shown to be efficacious and well tolerated. Two additional DPP-4 inhibitors are under review, and there are several others in clinical development. This article gives an overview on the mechanism of action of DPP-4 inhibitors and focuses on their development and their important physiological actions with regard to the treatment of type 2 diabetes.
Thornberry
Nancy A
NA
Department of Metabolic Disorders, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA.
Gallwitz
Baptist
B
D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D054795:Incretins; D007328:Insulin / Q000097:blood; D009570:Nitriles / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000627:therapeutic use; D000077597:Vildagliptin
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D054795:Incretins; D007328:Insulin; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D014230:Triazoles; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D018819:Dipeptidyl Peptidase 4; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate