Therapeutic assessment of glucagon-like peptide-1 agonists compared with dipeptidyl peptidase IV inhibitors as potential antidiabetic drugs.
The most prevalent form of diabetes is non-insulin-dependent or Type 2 diabetes. Innovative strategies to enhance insulin secretion and thereby improve glucose tolerance in patients with this type of diabetes are currently under preclinical and clinical investigation. These therapies include the applications of incretin hormones; gut hormones released postprandially that stimulate insulin secretion in pancreatic beta-cells. Because incretin actions are rapidly terminated by N-terminal cleavage of these peptide hormones by the amino-peptidase dipeptidyl peptidase IV (DPP IV, CD26), the utility of DPP IV inhibitors for the treatment of Type 2 diabetes is also under investigation. This review compares the therapeutic potential and possible side effects of metabolically stable analogues/peptide agonists of the incretin glucagon-like peptide-1 (GLP-1) with the application of DPP IV inhibitors that reduce the rate of endogenous degradation of GLP-1 and other incretins. GLP-1 analogues have been shown to be highly efficacious in the treatment of Type 2 diabetes, with minimal side effects. Of particular importance is the fact that they do not induce hypoglycaemia. However, they are currently available only in an injectable form. In contrast, DPP IV inhibitors have the clear advantage of oral application resulting in better patient compliance. Furthermore, they also potentiate the actions of other incretins normally degraded by the action of DPP IV. However, they possess more potential side effects. Taken together, both approaches offer promising new drugs for the treatment of Type 2 diabetes.
Mentlein
Rolf
R
University of Kiel, Anatomisches Institut, Olshausenstrasse 40, Kiel, Germany. rment@anat.uni-kiel.de
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4