Clinical pharmacology of alogliptin, a dipeptidyl peptidase-4 inhibitor, for the treatment of Type 2 diabetes

Alogliptin is a new, potent, highly selective, orally available inhibitor of the dipeptidyl peptidase-4 (DPP-4) enzyme developed for the treatment of Type 2 diabetes mellitus (T2DM). Inhibition of the DPP-4 enzyme, prevents the inactivation of the incretin hormones, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP), both of which have very short half-lives. GLP-1 and GIP are released in response to food ingestion; they enhance nutrient-induced insulin secretion and inhibit postprandial glucagon secretion. The pharmacokinetics and pharmacodynamics of alogliptin are suitable for once-daily dosing. In two Phase I clinical trials, one in healthy subjects and one in early-diagnosed patients with T2DM, alogliptin has been shown to be safe and well tolerated. In a Phase II clinical trial, alogliptin was shown to be safe and demonstrated efficacy in patients with T2DM with a dose–response profile suitable for Phase III dose selection.