Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus.
OBJECTIVE
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.


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 (HbA1c) from baseline.


RESULTS
After 16 weeks, 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 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 HbA1c at week 16 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).
Sportology Center Juntendo University Graduate School of Medicine Supported by High Technology Research Center Tokyo Japan.
Ryuzo
R
Kawamori
Department of Medicine Kawasaki Medical School Okayama Japan.
Kohei
K
Kaku
Department of Internal Medicine (I) Osaka Medical College Osaka Japan.
Toshiaki
T
Hanafusa
Dainippon Sumitomo Pharma Co., Ltd Osaka Japan.
Tatsuya
T
Oikawa
Division of Clinical Pharmacology and Therapeutics The Jikei University School of Medicine Tokyo Japan.
Shigeru
S
Kageyama
Japan Labor, Health and Welfare Organization Chubu Rosai Hospital Nagoya Japan.
Nigishi
N
Hotta
Combination therapy; Metformin; Repaglinide