小剂量罗格列酮与磺脲类降糖药联用治疗2型糖尿病的Ⅱ期临床试验

The Addition of Rosiglitazone to Sufonylureas Improves Glycemic Control in Patientswith Type 2 Diabetes:A Phase Two Clinical Trial in Chinese Populations.

目的 观察国产马来酸罗格列酮片治疗2型糖尿病的临床疗效及安全性。方法:多中心的临床研究,根据给药方案,按双盲、随机、平行、对照的原则进行分组。研究对象为在饮食控制、适当运动及已经使用磺脲类药物治疗1个月基础上,血糖控制不佳的2型糖尿病患者。原治疗方案与用药剂量不变,加用罗格列酮 4mg每日一次为试验组,加用二甲双胍0.25g每日二次为对照组,疗程均为12周。试验前后均进行空腹及餐后2h的血糖和胰岛素、糖化血红蛋白、血生化、血脂等检查。结果:共198例2型糖尿病患者进入疗效统计,其中,试验组102例,对照组96例。罗格列一磺脲类药物联用及二甲双胍一磺脲类药物联用均明显降低(P＜0.01)糖化血红蛋白、空腹及餐后血糖,提高胰岛素敏感性。罗格列酮试验组降低糖化血红蛋白达1.09%,而二甲双胍对照组降低达0.95%。试验组使空腹血糖及餐后2h血糖比基础值分别下降 2.52mmol·L-1(25.0%)和5.63mmol·L-1(35.6%)(P＜0.01),对照组使空腹血糖及餐后2h血糖比基础值分别下降1.76mmol·L-1(17.7%)和 3.73mmol·L-1(23.8%)(P＜0.01)。罗格列酮试验组的总胆固醇、低密度脂蛋白胆固醇及高密度脂蛋白胆固醇的水平均有显著意义的增高,而总胆固醇/高密度脂蛋白比值和低密度脂蛋白/高密度脂蛋白比值无变化。未见肝功能?

OBJECTIVE: To evaluate the efficacy and safety of low dose rosiglitazonetherapy combined with sulfonylureas in patients whose type 2 diabetes isinadequately controlled with sulfonylureas alone.METHOD:A multi-center double-blind, randomized, parallel, with metformin-sulfonylureas controlled clinical trial.Patients were assigned to receive 4mg.d-1 of rosiglitazone plus previous dosage ofsulfonylureas (n=l02) or 0.25g twice daily of metformin plus previous dosage ofsulfonylureas (n=96) for 12 weeks. Plasma glucose, glycosylated hemoglobin(HbAlc), insulin were tested and compared between baseline and 12 weeks.RESULTS: Glycosylated hemoglobin levels, fasting plasma glucose levels andinsulin action improved significantly with sulfonylureas-rosiglitazone therapy andsulfonylureas - metformin therapy. The mean levels of glycosylated hemoglobindecreased by 1.09% in the 4mg.d-1 sulfonylureas-rosiglitazone group (test group)and by 0.95% in the 0.25g/bid sulfony lureas - metformin group (control group ). Fasting and postprandial plasmaglucose levelsof the test group decreased by 2.52mmol.L-l (25.0%) and 5.63 mmol/L(35.6%) compared with the baseline (P<0.00l for all). Ofthe control group, fasting and postprandial plasma glucose levels decreased by l.76 mmol.L-1(l7.7%) and 3.73 mmol.L-1(23.8%)compared with the baseline (P<0.00l for all).Increase in total and low-density lipoprotein cholestero1 levels accompanied withincrease in high-density lipoprotein cho1esterol were observed (P<0.0l for test group taking rosiglitazone at week l2 vsbaseline) in the test group. The proportion of patients reporting adverse experiences was comparable between two groups.CONCUSIONS. Our data suggest that combination treatment with 4mg once-daily rosiglitazone plus previous dosage ofsulfonylureas in patients whose type 2 diabetes is inadequately controlled with sulfonylureas alone can improve g1ycemiccontrol, decrease insulin, hence improve insulin sensitivity, which is more effective than treatment with 0.25g twice-dailymetformin plus previous dosage of sulfonylureas. There is no liver damage been found.