Efficacy and safety of repaglinide vs nateglinide for treatment of Japanese patients with type 2 diabetes mellitus

Aims/Introduction: Repaglinide is a short‐acting insulin secretagogue. We assessed the efficacy and safety of repaglinide in comparison with nateglinide in Japanese patients with type 2 diabetes previously treated with diet and exercise. Materials and Methods: In this 16‐week randomized, multicenter, double‐blind, parallel‐group, active‐controlled superiority trial, Japanese patients with type 2 diabetes and glycated hemoglobin (HbA(1c)) of ≥6.9 and ≤9.4% were enrolled. Patients were randomly assigned to receive 0.5 mg repaglinide (n = 64) or 90 mg nateglinide (n = 66) three times a day. The primary end‐point was changes in HbA(1c) from baseline to the end of treatment. Results: Mean reductions of HbA(1c) were significantly greater for the repaglinide group than the nateglinide group (−1.17 ± 0.62 vs −0.81 ± 0.39%, P < 0.001). The target HbA(1c) values of <6.9% were achieved by 75.0% of the repaglinide group vs 59.1% for nateglinide. Mean changes in fasting plasma glucose also showed significantly greater efficacy for repaglinide than nateglinide (−26.0 ± 20.9 vs −18.3 ± 17.8 mg/dL, P < 0.001). There were no differences in the adverse event rates between the repaglinide and the nateglinide group, by 57.8% (37/64) and 60.6% (40/66), respectively. Incidences of hypoglycemic symptoms were 17.2% (11/64, 28 events) in the repaglinide group and 6.1% (4/66, 20 events) in the nateglinide group, respectively. Conclusions: In type 2 diabetic patients treated with diet and exercise, repaglinide monotherapy gives greater glycemic improvement than nateglinide monotherapy in reducing HbA(1c) and fasting plasma glucose values after 16 weeks. This trial was registered with JapicCTI (no. JapicCTI‐080521). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00188.x, 2011)