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

Abstract

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.

Keywords::

• alogliptin
• diabetes
• dipeptidyl peptidase-4
• incretin hormones

Financial & competing interests disclosure

Ronald Christopher is an employee of Takeda San Diego and Aziz Karim is an employee of Takeda Global Research & Development, Inc. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. Thanks to Michelle Kujawski, an employee of Takeda Pharmaceuticals North America, Inc., for writing and editorial support.