Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes
Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes
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DOI：
10.2337/dc06-0703
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发表时间：
2006-12-01
期刊：
影响因子：
16.2
通讯作者：
Williams-Herman, Debora E.
中科院分区：
文献类型：
--
作者：
Aschner, Pablo;Kipnes, Mark S.;Williams-Herman, Debora E.
目的：研究每日一次口服西格列汀单药治疗2型糖尿病患者的疗效和安全性。研究设计和方法--在一项随机、双盲、安慰剂对照研究中，（基线HbA（1c）[A1 C] 8.0%）随机分配至西格列汀100或200 mg或安慰剂组，持续24周。（P < 0.001）A1 C（分别为-0.79和-0.94%）和空腹血糖（分别为-1.0 mmol/l [-17.1 mg/dl]和-1.2 mmol/l [-21.3 mg/dl]）的安慰剂减去降低。基线A1 C>= 9%的患者在接受西格列汀100和200 mg治疗后，其减去安慰剂后的A1 C降幅（分别为-1.52和-1.50%）大于基线A1 C < 8%（分别为-0.57和-0.65%）或>= 8至< 9.0%（分别为-0.80和-1.13%）的患者。在膳食耐量试验中，西格列汀100和200 mg显著降低餐后2小时血糖（PPG）（减去安慰剂的PPG分别为-2.b mmol/l [-46.7 mg/dl]和-3.0 mmol/l [-54.1 mg/dl]）。上述关键疗效参数的结果在西格列汀剂量之间无显著差异。稳态模型评估的p-细胞功能和胰岛素原/胰岛素比值在西格列汀治疗后得到改善。低血糖的发生率相似，西格列汀组的总体胃肠道不良事件略高。西格列汀100 mg（-0.2 kg）或200 mg（-0.1 kg）组未观察到有意义的体重较基线变化。安慰剂组的体重变化（-1.1 kg）与西格列汀组的体重变化有显著性差异（P < 0.01）。结论：在这项为期24周的研究中，每日一次西格列汀单药治疗改善了空腹和餐后状态下的血糖控制，改善了β细胞功能的测量，2型糖尿病患者耐受性良好。
OBJECTIVE - To examine the efficacy and safety of once-daily oral sitagliptin as monotherapy in patients with type 2 diabetes. RESEARCHDESIGN AND METHODS - in a randomized, double-blind, placebo-controlled study, 741 patients (baseline HbA(1c) [A1C] 8.0%) were randomized to sitagliptin 100 or 200 mg or placebo for 24 weeks.RESULTS- Sitagliptin 100 and 200 mg produced significant (P < 0.001) placebo-subtracted reductions in A1C (-0.79 and -0.94%, respectively) and fasting plasma glucose (-1.0 mmol/l [-17.1 mg/dl] and -1.2 mmol/l [-21.3 mg/dl], respectively). Patients with baseline A1C >= 9% had greater reductions in placebo-subtracted A1C with sitagliptin 100 and 200 mg (- 1.52 and - 1.50%, respectively) than those with baseline A1C < 8% (-0.57 and -0.65%) or >= 8 to < 9.0% (-0.80 and -1.13%, respectively). In a meal tolerance test, sitagliptin 100 and 200 mg significantly decreased 2-h postprandial glucose (PPG) (placebo-subtracted PPG -2.b mmol/l [-46.7 mg/dl] and -3.0 mmol/l [-54.1 mg/dl], respectively). Results for the above key efficacy parameters were not significantly different between sitagliptin doses. Homeostasis model assessment of p-cell function and proinsulin-to-insulin ratio improved with sitagliptin. The incidence of hypoglycemia was similar, and overall gastrointestinal adverse experiences were slightly higher with sitagliptin. No meaningful body weight changes from baseline were observed with sitagliptin 100 (-0.2 kg) or 200 mg (-0.1 kg). The body weight change with placebo (-1.1 kg) was significantly (P < 0.01) different from that observed with sitagliptin.CONCLUSIONS - In this 24-week study, once-daily sitagliptin monotherapy improved glycemic control in the fasting and postprandial states, improved measures of beta-cell function, and was well tolerated in patients with type 2 diabetes.