title: Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin compared with alpha-glucosidase inhibitor in Japanese patients with type 2 diabetes inadequately controlled on metformin or pioglitazone alone (Study for an Ultimate Combination Therapy to Control Diabetes with Sitagliptin-1): A multicenter, randomized, open-label, non-inferiority trial.
abstract: OBJECTIVE
  To assess the efficacy and safety of sitagliptin compared with α-glucosidase inhibitors in Japanese patients with type 2 diabetes inadequately controlled by metformin or pioglitazone alone.
  
  
  METHODS
  In the present multicenter, randomized, open-label, parallel-group, active-controlled, non-inferiority trial, 119 patients aged 20-79 years with type 2 diabetes who had glycated hemoglobin 6.9-8.8% on stable metformin (500-1,500 mg/day) or pioglitazone (15-30 mg/day) alone were randomly assigned (1:1) to receive the addition of sitagliptin (50 mg/day) or an α-glucosidase inhibitor (0.6 mg/day voglibose or 150 mg/day miglitol) for 24 weeks. The primary end-point was change in glycated hemoglobin from baseline to week 12. All data were analyzed according to the intention-to-treat principle.
  
  
  RESULTS
  After 12 weeks, reductions in adjusted mean glycated hemoglobin from baseline were -0.70% in sitagliptin and -0.21% in the α-glucosidase inhibitor groups respectively; between-group difference was -0.49% (95% confidence interval -0.66 to -0.32, P < 0.0001), meeting the predefined non-inferiority criterion (0.25%) and showing statistical significance. This statistical significance also continued after 24 weeks. Although sitagliptin did not affect bodyweight, α-glucosidase inhibitors decreased bodyweight significantly from baseline (-0.39 kg; P = 0.0079). Gastrointestinal disorders were significantly lower with sitagliptin than with an α-glucosidase inhibitor (6 [10.3%] patients vs 23 [39.7%]; P = 0.0003). Minor hypoglycemia occurred in two patients (3.5%) in each group.
  
  
  CONCLUSIONS
  Sitagliptin showed greater efficacy and better tolerability than an α-glucosidase inhibitor when added to stable doses of metformin or pioglitazone. These findings support the use of sitagliptin in Japanese patients with type 2 diabetes inadequately controlled by insulin-sensitizing agents. This trial was registered with UMIN (no. 000004675).
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine Chiba, Japan ; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan ; Chiba University Hospital Clinical Research Center Chiba, Japan.
authors: Hidetaka
authors: H
authors: Yokoh
authors: Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan ; Department of Regional Disaster Medicine, Chiba University Graduate School of Medicine Chiba, Japan.
authors: Kazuki
authors: K
authors: Kobayashi
authors: Chiba University Hospital Clinical Research Center Chiba, Japan.
authors: Yasunori
authors: Y
authors: Sato
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine Chiba, Japan ; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan.
authors: Minoru
authors: M
authors: Takemoto
authors: Hotaruno Central Clinic Chiba, Japan.
authors: Daigaku
authors: D
authors: Uchida
authors: Chiba Central Medical Center Chiba, Japan.
authors: Azuma
authors: A
authors: Kanatsuka
authors: Misaki Naika Clinic Chiba, Japan.
authors: Nobuichi
authors: N
authors: Kuribayashi
authors: Chiba Aoba Municipal Hospital Chiba, Japan.
authors: Takashi
authors: T
authors: Terano
authors: Tokyo Women's Medical University Yachiyo Medical Center Chiba, Japan.
authors: Naotake
authors: N
authors: Hashimoto
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine Chiba, Japan ; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan.
authors: Kenichi
authors: K
authors: Sakurai
authors: Chiba University Hospital Clinical Research Center Chiba, Japan.
authors: Hideki
authors: H
authors: Hanaoka
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine Chiba, Japan ; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan.
authors: Ko
authors: K
authors: Ishikawa
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine Chiba, Japan ; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan.
authors: Shunichiro
authors: S
authors: Onishi
authors: Department of Clinical Cell Biology and Medicine, Chiba University Graduate School of Medicine Chiba, Japan ; Department of Diabetes, Metabolism and Endocrinology, Chiba University Hospital Chiba, Japan.
authors: Koutaro
authors: K
authors: Yokote
keywords: Alpha-glucosidase inhibitor; Combination drug therapy; Sitagliptin