Efficacy and safety between two dosages of gliclazide modified release tablets (30 mg and 60 mg once daily)in the treatment of patients with newly diagnosed type 2 diabetes

Abstract

Objective To evaluate the efficacy and safety of two dose levels of gliclazide MR (30 mg/d and 60 mg/d)in the treatment of Chinese patients with newly diagnosed type 2 diabetes mellitus (T2DM), and its effects on insulin resistance and β-cell function. Methods A total of 120 subjects with newly diagnosed T2DM were randomized to receive 30 mg/d (Group 30 mg)or 60 mg/d (Group 60 mg)of gliclazide MR in the proportion of 1 to 1 according to random number table for 16 weeks. Glycated hemoglobin A1c (HbA1c)was measured as major efficacy index, and secondary indices such as fasting plasma glucose (FPG), two-hour postprandial plasma glucose (2 h PG), 7-point glucose profile, area under curve of insulin (AUCINS), insulin sensitivity index (SEN) and the indices of the β-cell secretory function [including early insulin secretion index (ΔI30/ΔG30) , basic insulin secretion index (HOMA-β)and modified β- cell function (MBCI)]. Safety was assessed by adverse events (AEs), and so on. The difference of the measurement data was compared with the t test. The Wilcoxon test was used to assess the statistical difference among the groups. Results At 16 weeks, the change from baseline in HbA1c was -1.2%±1.1% in the Group 30 mg and -2.2%±1.4% in the Group 60 mg, intergroup comparison with baseline HbA1c as a covariate showed that the descent range in the Group 60 mg was more significant (F=4.2, P=0.04). There was no intergroup difference in the change from baseline of FPG, 2 hPG and 7-point glucose profile. Also, no intergroup difference was noted in the change from baseline of AUCINS and ΔI30/ΔG30. After treatment, the index of HOMA-β had a significant increasing amplitude in the Group 60 mg compared to that in the Group 30 mg (t=1951.0, P=0.04). The incidence of hypoglycemia related to study drug was 10.5% (6/57)in the Group 30 mg and 16.1%(9/56) in the Group 60 mg. To the end of follow-up, no significant difference in the body mass index was found between the two groups[(24.8±2.6) kg/m2 in Group 30 mg and (24.2±2.5) kg/m2 in Group 60 mg, t=1.09, P>0.05]. Conclusion The dose regimen of gliclazide MR 60 mg/d is superior to 30 mg/d in the improvement of HbA1c and β-cell function for Chinese patients with newly diagnosed T2DM; however, dosage of 60 mg/d increases the incidence of slight hypoglycemia events. Thus, for patients with newly diagnosed T2DM, selection of initial therapy dose should be patient- tailored, based on clinical features of β cell function and hypoglycemia risks. Key words: Diabetes mellitus, type 2; Gliclazide modified release; Treatment outcome; Safety