Efficacy and safety of alogliptin in Japanese patients with type 2 diabetes mellitus: a randomized, double-blind, dose-ranging comparison with placebo, followed by a long-term extension study

OBJECTIVE: To compare the efficacy and safety of different dosages of alogliptin with that of placebo and voglibose in drug-naïve Japanese patients with type 2 diabetes inadequately controlled by diet and exercise. RESEARCH DESIGN AND METHODS: In the double-blind, placebo-controlled phase of this two-part study, 480 patients aged ≥20 years with type 2 diabetes mellitus (HbA1c ≥6.9% to <10.4%) were randomized to monotherapy with alogliptin 6.25, 12.5, 25 or 50 mg once daily, placebo, or voglibose 0.2 mg three times daily for a period of 12 weeks. In a subsequent open-label, long-term extension phase, patients continued on the same treatment for an additional 40 weeks (patients in the placebo group were reassigned equally to one of the four alogliptin dosages). MAIN OUTCOME MEASURES: The primary efficacy endpoint was the change in HbA1c from the baseline value at week 12 of treatment. Safety endpoints were the occurrence of adverse events, vital sign measurements, physical examination and ECG findings, and laboratory test results recorded over the entire 52-week period. RESULTS: HbA1c was dose-dependently reduced by alogliptin, and the changes versus baseline were statistically significant with all four dosages in comparison with both placebo and voglibose. In addition, changes in fasting plasma glucose and postprandial plasma glucose AUC(0-2h) values were significantly greater with all four dosages of alogliptin in comparison with placebo. The incidence of adverse events with alogliptin over 52 weeks was not dose-dependent and was lower than with voglibose. Hypoglycemia occurred infrequently and was generally rated as mild. Changes in body weight with alogliptin were minimal (<0.5 kg) and not clinically meaningful. CONCLUSIONS: Alogliptin was well tolerated and dose-dependently improved glycemic parameters in patients with type 2 diabetes inadequately controlled on diet and exercise.