Sitagliptin improved glycemic control and was well tolerated when added to voglibose monotherapy in patients with type 2 diabetes

Results: Patients (pts) with type 2 diabetes (T2DM) frequently do not achieve glycemic goals with single oral antihyperglycemic agents (AHAs), and often require the use of combination therapy. The efficacy and safety of sitagliptin (SITA), an oral, highly-selective DPP-4 inhibitor, as monotherapy or when added to metformin, thiazolidinediones, or sulfonylureas, have been demonstrated; however, the effect of SITA added to an α-glucosidase inhibitor (AGI), an AHA class commonly used in Asian countries, has not been studied. This 12-week (wk), randomized, double-blind (DB), placebo (PBO)-controlled study in Japanese pts with T2DM assessed the efficacy and safety of SITA added to ongoing voglibose (VOG), an AGI widely used in Japan. Pts on VOG alone or in combination with other AHAs entered the screening period. Pts on VOG + other AHAs washed off of other AHAs for ≥8-wk prior to randomization. After a 2-wk single-blind PBO period, 133 pts (hemoglobin A1c [A1C] 6.5-10.0%) on a stable dose of VOG (0.2-0.3 mg TID) ≥12 wk and diet/exercise ≥12 wk, were randomized to the addition of SITA 50 mg QD (N=70; mean baseline A1C=7.5%) or PBO (N=63; mean baseline A1C=7.5%). The primary endpoint was A1C change from baseline at Wk 12. The efficacy analysis was based on the full analysis set using a constrained longitudinal data analysis model. At Wk 12, SITA added to VOG significantly (p<0.001) reduced mean A1C, fasting plasma glucose, and 2-hour postmeal glucose relative to PBO by 0.9%, 22.5 mg/dL, and 51.3 mg/dL, respectively. HOMA-β significantly increased with SITA relative to PBO (p<0.001), consistent with improved β-cell function. The incidences of adverse experiences (AEs) overall, serious AEs, drug-related AEs, gastrointestinal (GI) AEs, and hypoglycemia were similar between groups. Body weight was slightly reduced from baseline in both the SITA (0.33 kg) and PBO (0.47 kg) groups at Wk 12. In conclusion, in Japanese pts with T2DM and inadequate glycemic control on VOG monotherapy, the addition of SITA provided significant improvements in glycemic parameters and was generally well tolerated, with incidences of hypoglycemia and GI AEs similar to PBO.