Type 2 diabetes--therapy with dipeptidyl peptidase IV inhibitors.
The sole application of an inhibitor of the dipeptidyl peptidase DP IV (also DP 4, CD26, DPP-IV or DPP-4) to a mammal subsequently leading to improved glucose tolerance marks a major breakthrough in metabolic research bearing the potential of a new revolutionary diabetes therapy. This was demonstrated in rat applying the specific DP IV inhibitor isoleucyl thiazolidine. It was published in 1996 for the first time that a specific DP IV inhibitor in a given dose was able to completely block glucagon-like peptide-1 (GLP-1) degradation in vivo resulting in improved insulin response accompanied, by accelerated peripheral glucose disposal. Later on, these results were confirmed by several research teams applying DP IV inhibitors intravenously or orally. Today, the DP IV inhibition for the treatment of metabolic disorders is a validated principle. Now, more than 10 years after the initial animal experiments, first DP IV inhibitors as investigational drugs are tested in phase 3 clinical trials.
Demuth
Hans-Ulrich
HU
Probiodrug AG, Biocenter, Weinbergweg 22, D-06120 Halle (Saale), Germany. hans-ulrich.demuth@probiodrug.de
McIntosh
Christopher H S
CH
Pederson
Raymond A
RA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D017322:Clinical Trials, Phase II as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011759:Pyrrolidines / Q000627:therapeutic use; D051381:Rats; D013379:Substrate Specificity; D013844:Thiazoles / Q000627:therapeutic use; D014970:Xanthines / Q000627:therapeutic use
D001786:Blood Glucose; D008565:Membrane Proteins; D011480:Protease Inhibitors; D011759:Pyrrolidines; D013844:Thiazoles; D014970:Xanthines; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D018819:Dipeptidyl Peptidase 4