Double-blind, randomized, multicentre study of the efficacy and safety of gliclazide-modified release in the treatment of Chinese type 2 diabetic patients

Background and Aim: Gliclazide-modified release (gliclazide MR) is a new formulation of the sulfonylurea gliclazide designed for once-daily administration. The hydrophilic matrix of hypromellose-based polymer in the new formulation induces a progressive drug release, which parallels the 24-h glycaemic profile in type 2 diabetic patients. The aim of this study was to compare the efficacy and safety of gliclazide MR (once-daily administration) versus gliclazide (twice-daily administration) in Chinese type 2 diabetic patients. Materials and Methods: Sixty-three type 2 diabetic Chinese patients who had been on diet control alone or on treatment with metformin or on low dose of sulfonylurea were randomized to either gliclazide MR taken once daily or gliclazide taken twice daily. Dosage of metformin was maintained throughout the study, and the sulfonylurea was stopped. The dose of gliclazide MR was increased at 1-month intervals from 30 mg to 120 mg, while that of gliclazide from 80 mg to 320 mg until metabolic control was achieved [fasting plasma glucose (FPG) <= 7.7 mmol/l] or the maximum dose reached. Efficacy was mainly evaluated by levels of haemoglobin A1c (HbA1c) and FPG. Results: The mean baseline characteristics of the full analysis set 1 (FAS1) (HbA1c, n = 58) and the FAS2 (FPG, n = 61) were comparable in both groups. The levels of HbA1c decreased similarly in both groups over the treatment period: -1.6 +/- 1.6% (p < 0.001) on gliclazide MR (n = 31) and -1.6 +/- 1.4% (p < 0.001) on gliclazide (n = 27). Decrease in HbA1c was observed irrespective of pre-existing therapy for diabetes: -2.3 +/- 1.5% for patients on diet alone; -0.6 +/- 1.3% for patients switched from sulfonylurea to study drug and -1.4 +/- 0.8% for patients on metformin in combination with study drug. FPG decreased significantly from 177.5 +/- 63.5 to 136.7 +/- 42.2 (p < 0.001, n = 32) on gliclazide MR and not significant from 188.2 +/- 62.6 to 163.7 +/- 67.9 (p = 0.059, n = 29) on gliclazide. Both treatments were very well tolerated with no major hypoglycaemic episodes requiring external assistance; only three patients experienced mild hypoglycaemic episodes. Conclusions: Once-daily gliclazide MR showed a better trend in improving blood glucose control in comparison with gliclazide in type 2 diabetic Chinese patients irrespective of the pre-existing anti-diabetic treatment. The safety profiles of gliclazide MR and gliclazide were similar with a small number of patients having reported hypoglycaemic episodes. Once-daily dosing with gliclazide MR should improve patient compliance, an important factor in long-term glycaemic control.