薬理と治療

Abstract

Objective Saxagliptin is a novel, potent and selective inhibitor of dipeptidyl peptidase︱4. We performed two multicentre, randomized, placebo︱controlled, double︱blind, clinical studies to assess the efficacy and safety of saxagliptin in Japanese patients with type 2 diabetes mellitus. Methods In a PhaseⅡ dose︱response study, a total of 350 subjects were administered saxagliptin 1mg（n＝ 93）, 2.5 mg（n＝88）, or 5mg（n＝82）, or placebo（n＝87）once daily for 12 weeks. In a PhaseⅡ╱Ⅲ trial, 279 subjects were treated with saxagliptin monotherapy 2.5mg（n＝92）, 5 mg（n＝97）or placebo（n＝90）once daily for 24 weeks. The primary efficacy endpoint in the two trials was the change in HbA1c levels from baseline. Results In the dose︱response study, saxagliptin 1 mg, 2.5 mg, and 5mg significantly reduced HbA1c levels compared with placebo（P＜0.0001）. The mean change in HbA1c at Week 12 from baseline was －0.08, －0.59, －0.69, and －0.90％ in the placebo, saxagliptin 1 mg, 2.5mg and 5 mg groups, respectively. In the 24︱week trial, the reduction in HbA1c in the two saxagliptin monotherapy groups was significantly greater than that reported in the placebo group throughout the 24 weeks of treatment. The mean change in HbA1c at Week 24 from baseline was 0.27％, －0.25％, and －0.33％ in the placebo, saxagliptin 2.5 mg and saxagliptin 5 mg groups, respectively. No clinically significant adverse events, including hypoglycemia, were observed in the two trials. Conclusion The results of these two studies confirmed that saxagliptin monotherapy was effective and well tolerated in the treatment of Japanese patients with type 2 diabetes.