Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R
Dallas Diabetes and Endocrine Center at Medical City, 7777 Forest Lane, C-685, Dallas, TX 75230, USA.
Curr Med Res Opin. 2009 Oct;25(10):2401-11. doi: 10.1185/03007990903178735.
To evaluate the efficacy and safety of once-daily saxagliptin monotherapy in treatment-naïve patients with type 2 diabetes (T2D) and inadequate glycemic control.
This study included a main treatment cohort (MTC) with 401 patients (HbA(1c) > or = 7% and < or =10%) randomized and treated with oral saxagliptin 2.5, 5, or 10 mg once daily or placebo for 24 weeks and a separate open-label cohort (OLC) with 66 patients (HbA(1c) > 10% and < or =12%) who received saxagliptin 10 mg once daily for 24 weeks. Primary endpoint was HbA(1c) change from baseline to week 24. Secondary endpoints included change from baseline to week 24 in fasting plasma glucose (FPG), proportion of patients achieving HbA(1c) < 7%, and changes in postprandial glucose area-under-the-curve (PPG-AUC). Efficacy analyses for continuous variables were performed using an ANCOVA model with last-observation-carried-forward methodology.
In the MTC, saxagliptin demonstrated statistically significant decreases in adjusted mean HbA(1c) changes from baseline (mean, 7.9%) to week 24 (-0.43%, -0.46%, -0.54%) for saxagliptin 2.5, 5, and 10 mg, respectively, vs. +0.19% for placebo (all p < 0.0001). Adjusted mean FPG was significantly reduced from baseline (-15, -9, -17 mg/dL) for saxagliptin 2.5, 5, and 10 mg, respectively, vs. +6 mg/dL for placebo (p = 0.0002, p = 0.0074, p < 0.0001, respectively). More saxagliptin-treated patients achieved HbA(1c) < 7% at week 24 (35% [p = NS], 38% [p = 0.0443], 41% [p = 0.0133]) for saxagliptin 2.5, 5, and 10 mg, respectively, than placebo (24%). PPG-AUC was reduced for saxagliptin 2.5, 5, and 10 mg (-6868, -6896, -8084 mg x min/dL, respectively) vs. placebo (-647 mg x min/dL) with statistical significance demonstrated for saxagliptin 5 mg (p = 0.0002) and 10 mg (p < 0.0001). HbA(1c), FPG, and PPG-AUC reductions were also observed in the OLC at 24 weeks. In the MTC, adverse event frequency was similar across all study arms. No cases of confirmed hypoglycemia (symptoms, with fingerstick glucose < or =50 mg/dL) were observed in either cohort. Saxagliptin was not associated with weight gain. Study limitations included the lack of a control group for the OLC and the use of prespecified rescue criteria, which limited the exposure time during which patients could remain on their originally randomized medication without the introduction of additional antihyperglycemic rescue treatment.
Once-daily saxagliptin monotherapy for 24 weeks was generally well tolerated and demonstrated clinically meaningful reductions in key parameters of glycemic control vs. placebo.
Clinical Trials NCT00121641
评估每日一次的沙格列汀单药治疗对初治的2型糖尿病（T2D）且血糖控制不佳患者的疗效和安全性。
本研究包括一个主要治疗队列（MTC），401例患者（糖化血红蛋白[HbA₁c]≥7%且≤10%）被随机分组，接受每日一次口服2.5、5或10mg沙格列汀或安慰剂治疗24周；以及一个单独的开放标签队列（OLC），66例患者（HbA₁c>10%且≤12%）接受每日一次10mg沙格列汀治疗24周。主要终点是从基线到第24周HbA₁c的变化。次要终点包括从基线到第24周空腹血糖（FPG）的变化、HbA₁c<7%的患者比例以及餐后血糖曲线下面积（PPG-AUC）的变化。对连续变量的疗效分析使用协方差分析模型和末次观察结转法。
在MTC中，与安慰剂组的+0.19%相比，沙格列汀2.5mg、5mg和10mg组从基线（平均7.9%）到第24周调整后的平均HbA₁c变化有统计学显著降低（分别为-0.43%、-0.46%、-0.54%）（所有p<0.0001）。沙格列汀2.5mg、5mg和10mg组从基线开始调整后的平均FPG显著降低（分别为-15、-9、-17mg/dL），而安慰剂组为+6mg/dL（分别为p=0.0002、p=0.0074、p<0.0001）。在第24周，沙格列汀治疗的患者中达到HbA₁c<7%的比例更高，沙格列汀2.5mg、5mg和10mg组分别为35%（p=无统计学意义）、38%（p=0.0443）、41%（p=0.0133），高于安慰剂组的24%。沙格列汀2.5mg、5mg和10mg组的PPG-AUC降低（分别为-6868、-6896、-8084mg·min/dL），与安慰剂组（-647mg·min/dL）相比，沙格列汀5mg组（p=0.0002）和10mg组（p<0.0001）有统计学意义。在OLC中第24周也观察到HbA₁c、FPG和PPG-AUC降低。在MTC中，所有研究组的不良事件发生率相似。两个队列中均未观察到确诊的低血糖病例（有症状，指尖血糖≤50mg/dL）。沙格列汀与体重增加无关。研究局限性包括OLC缺乏对照组以及使用预先设定的挽救标准，这限制了患者在不引入额外降糖挽救治疗的情况下继续使用最初随机分配药物的暴露时间。
每日一次沙格列汀单药治疗24周总体耐受性良好，与安慰剂相比，在血糖控制的关键参数上有临床意义的降低。
临床试验NCT00121641
