Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in J apanese patients with type 2 diabetes mellitus

Aims/Introduction We investigated the efficacy and safety of repaglinide as an add‐on therapy for Japanese patients with type 2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500 mg/day, mainly) in addition to diet and exercise. Materials and methods In the 16‐week multicenter, placebo‐controlled, randomized, double‐blind, parallel‐group trial (the phase  III study), patients with type 2 diabetes mellitus with metformin monotherapy were randomly assigned to the repaglinide or placebo group. Thereafter, a 36‐week, multicenter, uncontrolled, dose‐titration method study was extended to a total duration of 52 weeks (the long‐term study). The primary end‐point of each study was a change in glycated hemoglobin (HbA 1c ) from baseline. Results After 16 weeks, mean reductions in HbA 1c were significantly greater for the repaglinide group than for the placebo group (–0.98 ± 0.72% vs 0.13 ± 0.63%, P  < 0.001). In the long‐term study, the mean change in HbA 1c was −0.76 ± 0.83%. The rate of adverse events was 60.6 and 50.0% in the repaglinide and placebo groups, respectively, in the phase  III study, and 78.3% in the long‐term study. Hypoglycemia was reported in 11.7, 0 and 13.3% of patients in the repaglinide group, placebo group and long‐term study, respectively. Conclusions Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA 1c at week 16 and in a significant long‐term improvement in HbA 1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with Japic CTI (nos. Japic CTI ‐101202 and Japic CTI ‐101203).