Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type2 diabetes mellitus.

Abstract

We investigated the efficacy and safety of repaglinide as an add-on therapy for Japanese patients with type2 diabetes mellitus receiving metformin monotherapy (at a dose of 1,500mg/day, mainly) in addition to diet and exercise. In the 16-week multicenter, placebo-controlled, randomized, double-blind, parallel-group trial (the phaseIII study), patients with type2 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 52weeks (the long-term study). The primary end-point of each study was a change in glycated hemoglobin (HbA1c) from baseline. After 16weeks, mean reductions in HbA1c 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 HbA1c 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 phaseIII 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. Combination therapy with repaglinide and metformin resulted in an approximately 1% reduction in HbA1c at week16 and in a significant long-term improvement in HbA1c at the end of the study. No safety problems were noted during the concomitant use of repaglinide and metformin. These studies were registered with JapicCTI (nos. JapicCTI-101202 and JapicCTI-101203).