The therapeutic actions of DPP-IV inhibition are not mediated by glucagon-like peptide-1

Excerpt

Glucagon-like peptide 1 (GLP-1) and its derivatives have generated considerable interest [1]. GLP-1 has the potential to normalise glucose concentrations in patients with type 2 diabetes; however, this peptide hormone is degraded and eliminated from the circulation too rapidly to be of therapeutic value. The initial step of proteolytic cleavage and inactivation is mediated by dipeptidyl peptidase-IV (DPP-IV), following which, only 10–15% of the peptide remains in its intact, biologically active form during the continuous infusion of GLP-1 [2]. DPP-IV inhibitors reverse this effect, increasing circulating levels by a factor of 4–6 during the infusion of exogenous GLP-1 [3], thus providing the rationale for their use in diabetes therapy. Phase II studies have shown that DPP-IV inhibitors can lower HbA₁c levels by approximately 1%, thus confirming their therapeutic potential [4]. …