Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai Clinical Center for Endocrine and Metabolic Diseases, 197 Ruijin 2nd Road, Shanghai 200025, China.
Expert Opin Pharmacother. 2011 Dec;12(18):2791-9. doi: 10.1517/14656566.2011.602341. Epub 2011 Jul 22.
The aim of this research is to determine efficacy and safety of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy.
A 16-week, open-label, randomized, active-controlled, parallel-group trial was carried out. Subjects were randomized (1:1) to repaglinide 1 mg t.i.d. (maximum dose, 4 mg t.i.d.) or repaglinide plus metformin 1 mg/500 mg t.i.d. (maximum dose, 4 mg/500 mg t.i.d.). Eligible subjects (18 - 75 years old) had type 2 diabetes, A1C > 8.5%, BMI ≤ 35 kg/m(2), and were naive to oral antidiabetes agents.
The primary outcome was A1C reduction. Secondary end points included fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and 7-point plasma glucose. Baseline characteristics (repaglinide/metformin, n = 218; repaglinide-only, n = 214) were similar between groups. Mean A1C reduction (± SD) was 4.51 ± 1.64% (combination) and 4.05 ± 1.59% (monotherapy). Estimated mean treatment difference for repaglinide/metformin versus repaglinide-only was -0.30% (95% CI -0.49 to -0.11; p < 0.01). Combination treatment demonstrated significant improvements versus monotherapy in FPG, 7-point plasma glucose, and lunchtime and dinnertime 2-h PPG (all p < 0.05). Hypoglycemia rates were 2.04 (combination) versus 1.35 (monotherapy) events/subject-year (p = 0.058). Adverse events were comparable between groups.
Repaglinide plus metformin and repaglinide alone provided significant improvements in glycemic control and were well tolerated in Chinese patients naive to treatment with oral antidiabetes agents. Combination therapy with repaglinide plus metformin showed superiority to repaglinide monotherapy in this population. Limitations of this study are that subjects were newly diagnosed and had high mean baseline A1C, which may affect generalizability of results.
本研究旨在评估利拉鲁肽在中国 2 型糖尿病初治患者中的疗效和安全性。
这是一项为期 16 周、开放标签、随机、阳性对照、平行分组的临床试验。受试者按照 1:1 的比例随机分配至利拉鲁肽 1mg，每日三次（最大剂量 4mg，每日三次）或利拉鲁肽联合二甲双胍 1mg/500mg，每日三次（最大剂量 4mg/500mg，每日三次）。入选受试者（18-75 岁）为 2 型糖尿病患者，糖化血红蛋白（HbA1c）＞8.5%，体重指数（BMI）≤35kg/m²，且未接受过口服降糖药物治疗。
主要终点为 HbA1c 降幅。次要终点包括空腹血糖（FPG）、餐后 2 小时血糖（PPG）和 7 点血糖谱。两组间的基线特征（利拉鲁肽/二甲双胍组，n=218；利拉鲁肽单药组，n=214）相似。利拉鲁肽/二甲双胍组和利拉鲁肽单药组的平均 HbA1c 降幅分别为 4.51±1.64%和 4.05±1.59%。利拉鲁肽/二甲双胍组和利拉鲁肽单药组间的平均治疗差异为-0.30%（95%置信区间-0.49 至-0.11；p＜0.01）。与单药组相比，联合治疗组在 FPG、7 点血糖谱以及午餐和晚餐后 2 小时 PPG 方面均有显著改善（均 p＜0.05）。低血糖发生率分别为 2.04（联合治疗组）和 1.35（单药治疗组）事件/患者年（p=0.058）。两组不良反应发生率相似。
在初治中国 2 型糖尿病患者中，利拉鲁肽联合二甲双胍和利拉鲁肽单药均能显著改善血糖控制，且安全性良好。与利拉鲁肽单药治疗相比，利拉鲁肽联合二甲双胍治疗在该人群中显示出优越性。本研究的局限性在于受试者均为初诊患者，且基线 HbA1c 较高，这可能影响研究结果的普遍性。
