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/IntroductionTo assess the efficacy and safety of sitagliptin compared with -glucosidase inhibitors in Japanese patients with type2 diabetes inadequately controlled by metformin or pioglitazone alone. Materials and MethodsIn the present multicenter, randomized, open-label, parallel-group, active-controlled, non-inferiority trial, 119 patients aged 20-79years with type2 diabetes who had glycated hemoglobin 6.9-8.8% on stable metformin (500-1,500mg/day) or pioglitazone (15-30mg/day) alone were randomly assigned (1:1) to receive the addition of sitagliptin (50mg/day) or an -glucosidase inhibitor (0.6mg/day voglibose or 150mg/day miglitol) for 24weeks. The primary end-point was change in glycated hemoglobin from baseline to week12. All data were analyzed according to the intention-to-treat principle. ResultsAfter 12weeks, reductions in adjusted mean glycated hemoglobin from baseline were -0.70% in sitagliptin and -0.21% in the -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 24weeks. Although sitagliptin did not affect bodyweight, -glucosidase inhibitors decreased bodyweight significantly from baseline (-0.39kg; P=0.0079). Gastrointestinal disorders were significantly lower with sitagliptin than with an -glucosidase inhibitor (6 [10.3%] patients vs 23 [39.7%]; P=0.0003). Minor hypoglycemia occurred in two patients (3.5%) in each group. ConclusionsSitagliptin showed greater efficacy and better tolerability than an -glucosidase inhibitor when added to stable doses of metformin or pioglitazone. These findings support the use of sitagliptin in Japanese patients with type2 diabetes inadequately controlled by insulin-sensitizing agents. This trial was registered with UMIN (no. 000004675).