Type II diabetes - alogliptin
Type II diabetes is a growing global health problem, exacerbated by poor diets and increasingly sedentary lifestyles. The World Health Organisation estimates that in 2006 more than 180 million people had some form of diabetes, and this is expected to double in the next couple of decades.
Type II diabetes is a growing global health problem, exacerbated by poor diets and increasingly sedentary lifestyles. The World Health Organisation estimates that in 2006 more than 180 million people had some form of diabetes, and this is expected to double in the next couple of decades.
Many new treatments for the disease are in development, including Takeda's alogliptin, developed at US biotech Syrrx, now a subsidiary of Takeda.1 This is designed to increase insulin secretion from islet β-cells, which it does by inhibiting the serine protease compound dipeptidyl peptidase IV. This controls the incretin activity of glucagons-like peptide and glucose-dependent insulinotropic polypeptide; and inhibiting DPP-IV can increase the concentrations of both these peptides, and as a result enhance insulin secretion and improve glucose tolerance, as well as improve plasma glucose concentrations in Type II diabetes patients.
In a randomised, double blind, placebo-controlled Phase I study, 36 healthy, non-obese males were given 25, 50, 100, 200, 400 or 800mg of alogliptin or placebo.2 The drug was rapidly absorbed and slowly eliminated, primarily in the urine, and mean peak DPP-IV inhibition ranged from 93 to 99%, and a mean inhibition of 74 to 97% 24 hours after dosing. There was no apparent dose-response effect, and it was well tolerated. Five subjects - one from the placebo group - reported asymptomatic hypoglycaemia; other adverse events, experienced by single subjects, included dizziness, constipation and syncope.
A double blind, randomised, placebo-controlled trial has been carried out in a group of patients with Type II diabetes, 54 of whom completed the trial.3 Subjects were given 20, 100 or 400mg of the drug or placebo once a day for 14 days. The drug had a substantial inhibitory effect on DPP-IV, with peak inhibitions between 94% and 99% across all of the dose sizes on both days 1 and 14. Peak inhibition was achieved between 1 and 2.5 hours of dosing, and three days after the last dose mean inhibition varied from 66% to 82%.