Alogliptin: a new addition to the class of DPP-4 inhibitors

BACKGROUND: Alogliptin is an oral antihyperglycemic agent that is a selective inhibitor of the enzyme dipeptidyl peptidase-4 (DPP-4). Inhibition of DPP-4 elevates levels of the incretin hormones glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) by preventing their degradation. OBJECTIVE: To review the evolution of alogliptin and its pharmacokinetics, pharmacodynamics, clinical efficacy and adverse effects. In addition, we compared alogliptin to other DPP-4 inhibitors. METHODS: A comprehensive literature search was performed using the term ‘alogliptin’. Original research articles and review articles as well as scientific abstracts were included. RESULTS: Alogliptin raises postprandial levels of GLP-1. It has excellent bioavailability exhibiting a median T(max) ranging from 1 to 2 hours and a mean half-life of 12.4 to 21.4 hours across all doses. When given as monotherapy, mean hemoglobin A(1c) (HbA(1c)) reductions achieved were 0.5% to 0.6%. Combination therapy yielded similar reductions (−0.5% with metformin, −0.6% with glyburide, −0.8% with pioglitazone and −0.6% with insulin). Administration of alogliptin does not promote weight loss but has not resulted in weight gain. The agent is relatively well tolerated with few adverse effects, the major finding being a marginally higher rate of skin events, primarily pruritus. CONCLUSIONS: Alogliptin causes significant reductions in HbA(1c) when used alone or in combination with other oral agents in patients with type 2 diabetes similar to other DPP-4 inhibitors in current clinical use. The side effect profile also does not differ from that of other DPP-4 inhibitors. However, long-term studies are necessary before the place of alogliptin in the management of type 2 diabetes can be established.