Alogliptin, a highly selective dipeptidyl peptidase-IV (DPP-4) inhibitor under investigation for the treatment of type 2 diabetes, demonstrated efficacy in reducing glucose levels throughout the day, in an early phase clinical study.
Safety results for this multi-dose study showed that alogliptin was well tolerated in patients with type 2 diabetes, with an incidence of hypoglycemia similar to placebo. No serious adverse event was reported, and no dose-limiting toxicity was observed over the entire dose range of 25 to 400 mg. The data were announced during a poster presentation at the 67th Scientific Sessions of the American Diabetes Association (ADA) meeting in Chicago.
"These are encouraging early results for alogliptin as a potential new type 2 diabetes treatment to help manage glucose levels throughout the day,” said Qais A. Mekki, MD, PhD, vice president, Clinical Science at Takeda Global Research & Development, Inc. “Alogliptin is a reflection of Takeda's commitment to finding innovative options to help patients manage their type 2 diabetes.”
This was a randomized, double-blind, placebo-controlled, parallel-group, multi-dose study conducted in multiple centers. Subjects were patients with type 2 diabetes who were either newly diagnosed or treated with diet and exercise alone for the previous three months and were between the ages of 18 and 75 years.
The objectives of the study were to assess the uptake, utilization and metabolism, as well as the tolerability, of alogliptin after multiple-dose administration to patients with type 2 diabetes. The primary efficacy endpoint was change in mean 4-hour postprandial plasma glucose levels from Baseline (Day -1) to Day 14. Secondary efficacy endpoints included change in mean 4-hour postprandial insulin levels; fasting plasma levels of C-peptide, fructosamine, and glycosylated hemoglobin (A1C); and incidence of hyperglycemia (blood glucose =200 mg/dL).
Fifty-five patients were assigned to receive alogliptin 25 (n=15), 100 (n=14), or 400 mg (n=15), or placebo (n=11) once daily for 14 days. Patients received three standardized meals a day and a snack after dosing on Days -1 (Baseline), 1 and 14. Blood and urine samples were collected through 24 hours after Day 1 and through 48 hours after Day 14.
On Day 14, statistically significant decreases from Baseline in mean 4-hour plasma glucose levels were observed for 25, 100, and 400 mg doses, after each of three meals. These reductions were compared to those achieved by placebo:
- Breakfast: -39.9, -48.6, and -68.3 mg/dL, respectively
- Lunch: -30.5, -46.0, and -38.4 mg/dL, respectively
- Dinner: -35.1, -54.7, and -46.1 mg/dL, respectively
Alogliptin demonstrated rapid and sustained inhibition of plasma DPP-4 activity, across all doses: