Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone
Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone
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DOI：
10.2337/dc06-0706
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发表时间：
2006-12-01
期刊：
影响因子：
16.2
通讯作者：
Meininger, Gary
中科院分区：
文献类型：
--
作者：
Charbonnel, Bernard;Karasik, Avraham;Meininger, Gary
目的：在血糖控制不佳的2型糖尿病患者（HbA（1c）[A1 C] >= 7且：研究设计和方法-在筛选饮食/运动导入期、二甲双胍剂量滴定/稳定期和2周后，在单盲、安慰剂导入期，701例年龄19-78岁、轻度至中度高血糖（平均A1 C 8.0%）、正在接受二甲双胍（>= 1,500 mg/天）的患者被随机分配接受安慰剂或西格列汀100 mg，每日一次，比例为1：2，持续24周。超过特定血糖限值的患者接受补救治疗（吡格列酮），直至研究结束。疗效分析是基于所有患者治疗的人口使用ANCOVA和排除后获得的数据血糖rescue.RESULTS -在第24周，西格列汀治疗导致显着降低A1 C（-0.65%），空腹血糖和2小时餐后血糖与安慰剂相比。与安慰剂相比，西格列汀显著改善了空腹胰岛素、空腹C肽、空腹胰岛素原/胰岛素比值、餐后胰岛素和C肽曲线下面积（AUC）、餐后胰岛素AUC/葡萄糖AUC比值、P细胞功能稳态模型评估和定量胰岛素敏感性检查指数。西格列汀组A1 C < 7%的患者比例（47.0%）显著高于安慰剂组（18.3%）。与安慰剂相比，西格列汀未增加低血糖或胃肠道不良事件的风险。西格列汀和安慰剂组体重下降相似。结论-西格列汀100 mg每日一次加二甲双胍治疗对单用二甲双胍血糖控制不佳的2型糖尿病患者有效且耐受性良好。
OBJECTIVE - The efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, added to ongoing metformin therapy, were assessed in patients with type 2 diabetes who had inadequate glycemic control (HbA(1c) [A1C] >= 7 and: 10%) with metformin alone.RESEARCH DESIGN AND METHODS - After a screening diet/exercise run-in period, a metformin dose titration/stabilization period, and a 2-week, single-blind, placebo run-in period, 701 patients, aged 19-78 years, with mild to moderate hyperglycemia (mean A1C 8.0%) receiving ongoing metformin (>= 1,500 mg/day) were randomly assigned to receive the addition of placebo or sitagliptin 100 mg once-daily in a 1:2 ratio for 24 weeks. Patients exceeding specific glycemic limits were provided rescue therapy (pioglitazone) until the end of the study. The efficacy analyses were based on an all-patients-treated population using an ANCOVA and excluded data obtained after glycemic rescue.RESULTS - At week 24, sitagliptin treatment led to significant reductions compared with placebo in A1C (-0.65%), fasting plasma glucose, and 2-h postmeal glucose. Fasting insulin, fasting C-peptide, fasting proinsulin-to-insulin ratio, postmeal insulin and C-peptide areas under the curve (AUCs), postmeal insulin AUC-to-glucose AUC ratio, homeostasis model assessment of P-cell function, and quantitative insulin sensitivity check index were significantly improved with sitagliptin relative to placebo. A significantly greater proportion of patients achieved an A1C < 7% with sitagliptin (47.0%) than with placebo (18.3%). There was no increased risk of hypoglycemia or gastrointestinal adverse experiences with sitagliptin compared with placebo. Body weight decreased similarly with sitagliptin and placebo.CONCLUSIONS - Sitagliptin 100 mg once-daily added to ongoing metformin therapy was efficacious and well tolerated in patients with type 2 diabetes who had inadequate glycemic control with metformin alone.