Dutogliptin (PHX-1149T), being developed by Phenomix Corp, Forest Laboratories Inc and Chiesi Farmaceutici SpA, is a small-molecule dipeptidyl peptidase-4 (DPP-4) inhibitor for the potential oral treatment of
type 2 diabetes mellitus (T2DM). DPP-4 quickly degrades the
insulin secretory
hormones,
glucose-dependent insulinotropic peptide and
glucagon-like peptide-1; thus inhibiting the degradation of these
hormones is a viable treatment option for patients with T2DM. In preclinical studies,
dutogliptin potently inhibited DPP-4 and, in a model of T2DM, treatment with
dutogliptin improved
glucose homeostasis. Pharmacokinetic analyses in animals, healthy individuals and patients with T2DM demonstrated that
drug exposure increased in a dose-dependent manner. Results from phase II clinical trials indicated that once-daily
dutogliptin, in combination with other oral diabetes
therapies, reduces postprandial
blood glucose and HbA1c levels, both indicators of successful diabetes management. In phase I and II trials,
dutogliptin was safe, well tolerated and associated with extremely low rates of
hypoglycemia. At the time of publication, phase III trials were underway and the results of these will be imperative to determine the efficacy of
dutogliptin compared with other small molecule
DPP-4 inhibitors, such as
sitagliptin and
vildagliptin.