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

AIMS/INTRODUCTION: 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. MATERIALS AND 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).