二甲双胍格列吡嗪复方制剂治疗2型糖尿病的多中心随机、双盲临床试验

Glyburide/Metformin Therapy for Patients with Type 2 Diabets-a Multi-Center,Randomized Double-Masked Study

目的评价二甲双胍格列吡嗪复方制剂治疗2型糖尿病的疗效和安全性。方法多中心、随机、双盲双模拟临床试验,入选符合条件的2型糖尿病患者223例并随机分组:二甲双胍格列吡嗪组112例,盐酸二甲双胍组57例,格列吡嗪组54例,用药观察12周,观察糖化血红蛋白、静脉空腹血糖、餐后2 h血糖和空腹胰岛素变化,并通过不良事件、心电图和实验室检查分析进行安全性评价。结果与治疗前相比,治疗后复方制剂组的糖化血红蛋白[(6.9±1.2)%,治疗前(5.84±1.19)%]、空腹血糖水平[(8.68±1.69)mmol.L-1与治疗前(7.1±1.54)mmol.L-1]、餐后2 h血糖水平[(13.9±2.91)mmol.L-1与治疗前(10.85±3.15)mmol.L-1]均显著下降(P<0.000 1),且下降程度均明显高于2个对照组即二甲双胍组和格列吡嗪组(P<0.000 1);而以上疗效指标在对照组治疗前后并无显著差异;空腹胰岛素变化程度在3组间比较均无统计学意义。不良事件以胃肠道反应为主,组间比较差异无统计学意义。结论二甲双胍格列吡嗪复方制剂比单药治疗具有更好的降糖效果,且安全性好,临床推广将在提高患者用药依从性方面有独特优势。

OBJECTIVE To compare the efficacy and safety of a fixed combination of glyburide/metformin with those of glyburide or metformin alone in patients with type 2 diabetes. METHODS In this 12-week, randomized, double-blind, double-mimic study, 223 patients were randomly assigned to glyburide/metformin （n = 112 ） , metformin （n = 57 ） , or glyburide （n = 54 ） group. The primary outcome measures were HbA1 c level and fasting plasma glucose （FPG） level; secondary outcome measures included 2 h post-prandial plasma glucose （2hPG） and fasting plasma insulin levels. Adverse events were recorded. RESULTS Compared with the baseline, HbAlc [ （6. 9 ± 1.2）% vs （5.84 ± 1.19）% ] and FPG [ （8.68 ± 1.69） mmol ·L- 1vs （7. 1 ± 1.54） mmol ·L- 1 ] and 2hPG [ （ 13.9 ± 2. 91 ） mmol ·L- 1 vs （ 10. 85 ± 3.15 ） mmol ·L- 1 ] were all significantly lowered in the glyburide/metformin group （ P 〈 0. 000 1 ） , and they were reduced more in the combination group than in the two monotherapy groups （ P 〈 0. 000 1 ）. The changes in fasting plasma insulin concentrations were not significantly different among these three groups. The main adverse events were gastrointestinal side effects. Safety and tolerability were similar across all treatment groups. CONCLUSION Glyburide/metformin combination therapy produced better glycaemic control than monotherapy with mild adverse events and better compliance.