University of Liège, Division of Diabetes, Nutrition and Metabolic Disorders and Clinical Pharmacology Unit, CHU Liège, Liège, Belgium.
Diabetes Metab Res Rev. 2010 Oct;26(7):540-9. doi: 10.1002/dmrr.1114.
Dipeptidyl peptidase-4 inhibitors improve glycaemic control in patients with type 2 diabetes mellitus when used as monotherapy or in combination with other anti-diabetic drugs (metformin, sulphonylurea, or thiazolidinedione). This 18-week, phase 3b, multicentre, double-blind, noninferiority trial compared the efficacy and safety of two dipeptidyl peptidase-4 inhibitors, saxagliptin and sitagliptin, in patients whose glycaemia was inadequately controlled with metformin.
Adult type 2 diabetes mellitus patients (N = 801) with glycated haemoglobin (HbA(1c)) 6.5-10% on stable metformin doses (1500-3000 mg/day) were randomized 1 : 1 to add-on 5 mg saxagliptin or 100 mg sitagliptin once daily for 18 weeks. The primary efficacy analysis was a comparison of the change from baseline HbA(1c) at week 18 in per-protocol patients. Noninferiority was concluded if the upper limit of the two-sided 95% confidence interval of the HbA(1c) difference between treatments was < 0.3%.
The adjusted mean changes in HbA(1c) following the addition of saxagliptin or sitagliptin to stable metformin therapy were - 0.52 and - 0.62%, respectively. The between-group difference was 0.09% (95% confidence interval, - 0.01 to 0.20%), demonstrating noninferiority. Both treatments were generally well tolerated; incidence and types of adverse events were comparable between groups. Hypoglycaemic events, mostly mild, were reported in approximately 3% of patients in each treatment group. Body weight declined by a mean of 0.4 kg in both groups.
Saxagliptin added to metformin therapy was effective in improving glycaemic control in patients with type 2 diabetes mellitus inadequately controlled by metformin alone; saxagliptin plus metformin was noninferior to sitagliptin plus metformin, and was generally well tolerated.
二肽基肽酶-4 抑制剂(DPP-4i)单独使用或与其他抗糖尿病药物(二甲双胍、磺酰脲类或噻唑烷二酮类)联合使用,可改善 2 型糖尿病患者的血糖控制。本 18 周、3b 期、多中心、双盲、非劣效性试验比较了两种二肽基肽酶-4 抑制剂(西格列汀和沙格列汀)在血糖控制不佳的二甲双胍治疗患者中的疗效和安全性。
接受稳定剂量(1500-3000mg/天)二甲双胍治疗的糖化血红蛋白(HbA1c)为 6.5-10%的成年 2 型糖尿病患者(N=801),按 1:1 随机分组,加用每日 1 次 5mg 西格列汀或 100mg 沙格列汀,治疗 18 周。主要疗效分析为治疗 18 周时的 HbA1c 自基线的变化。如果两治疗组间 HbA1c 差值的双侧 95%置信区间上限<0.3%,则可判定非劣效性。
加用西格列汀或沙格列汀后,稳定的二甲双胍治疗的 HbA1c 分别降低 0.52%和 0.62%。组间差异为 0.09%(95%置信区间,-0.01 至 0.20%),表明非劣效性。两种治疗均具有良好的耐受性;两组间不良事件的发生率和类型相当。两组患者约 3%发生轻度低血糖事件。两组患者体重平均下降 0.4kg。
西格列汀联合二甲双胍治疗可有效改善单独使用二甲双胍血糖控制不佳的 2 型糖尿病患者的血糖控制,西格列汀联合二甲双胍与沙格列汀联合二甲双胍的疗效相当,且均具有良好的耐受性。