Factors associated with the glucose-lowering efficacy of sitagliptin in Japanese patients with type 2 diabetes mellitus: Pooled analysis of Japanese clinical trials

Aims/Introduction To explore the factors associated with the glucose-lowering efficacy of sitagliptin treatment in Japanese patients with type 2 diabetes mellitus. Materials and Methods This was a post-hoc analysis of pooled data from seven sitagliptin phase II and III clinical studies carried out in Japan. All studies were double-blind, randomized, placebo-controlled, parallel-group and of 12-week duration. The analysis population consisted of 1,075 type 2 diabetes mellitus patients. In two of the trials, sitagliptin 50 mg and/or 100 mg daily were used as monotherapy; in five others, sitagliptin 50 mg daily was used as add-on treatment to ongoing pioglitazone, glimepiride, metformin, voglibose or glinides. Efficacy (reduction in hemoglobin A1c [HbA1c]) was evaluated in 12 sets of subgroups defined by demographic, glycemic, pancreatic beta-cell function and insulin resistance parameters. An analysis of covariance model was used to evaluate the interaction between each parameter and efficacy. Results Sitagliptin consistently provided a clinically meaningful reduction in HbA1c relative to placebo across all subgroups. Within subgroups, a greater absolute HbA1c reduction was associated with higher baseline HbA1c, fasting plasma glucose and 2-h post-meal glucose. Lower beta-cell function, represented by homeostatic model assessment of beta-cell function and insulinogenic index, was also associated with greater HbA1c reduction. In contrast, age, sex, body mass index, duration of type 2 diabetes mellitus and insulin resistance-related parameters did not interact with HbA1c changes. Conclusions Sitagliptin treatment was associated with clinically meaningful improvement in glycemic control in all subgroups of Japanese patients with type 2 diabetes mellitus that were evaluated. Higher baseline glycemic status and lower baseline beta-cell function were identified as factors associated with greater HbA1c reduction after sitagliptin treatment.