Therapeutic assessment of glucagon-like peptide-1 agonists compared with dipeptidyl peptidase IV inhibitors as potential antidiabetic drugs

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Abstract
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 β-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 ...