Merck Research Laboratories, Rahway, NJ 07065, USA. debora
Diabetes Obes Metab. 2010 May;12(5):442-51. doi: 10.1111/j.1463-1326.2010.01204.x.
To assess the 104-week efficacy and safety of sitagliptin and metformin as initial combination therapy and as monotherapy in patients with type 2 diabetes and inadequate glycaemic control (HbA(1c) 7.5-11%) on diet and exercise.
This study was a 50-week, double-blind extension of a 54-week, randomized, double-blind, factorial study of the initial combination of sitagliptin and metformin, metformin monotherapy and sitagliptin monotherapy (104 weeks total duration). Patients assigned to active therapy in the 54-week base study remained on those treatments in the extension study: sitagliptin 50 mg b.i.d. + metformin 1000 mg b.i.d. (higher dose combination), sitagliptin 50 mg b.i.d. + metformin 500 mg b.i.d. (lower dose combination), metformin 1000 mg b.i.d. (higher dose), metformin 500 mg b.i.d. (lower dose) and sitagliptin 100 mg q.d. Patients randomized to receive the sequence of placebo/metformin were switched, in a blinded manner, from placebo to metformin monotherapy uptitrated to 1000 mg b.i.d. beginning at week 24 and remained on higher dose metformin through the extension.
Amongst patients who entered the extension study without having initiated glycaemic rescue therapy, least-squares mean changes in HbA(1c) from baseline at week 104 were -1.7% (higher dose combination), -1.4% (lower dose combination), -1.3% (higher dose), -1.1% (lower dose) and -1.2% (sitagliptin). The proportions of patients with an HbA(1c) <7% at week 104 were 60% (higher dose combination), 45% (lower dose combination), 45% (higher dose), 28% (lower dose) and 32% (sitagliptin). Fasting and postmeal measures of glycaemic control and beta-cell function improved in all groups, with glycaemic responses generally maintained over the 104-week treatment period. The incidence of hypoglycaemia was low across all groups. The incidences of gastrointestinal adverse experiences were generally lower in the sitagliptin group and similar between the metformin monotherapy and combination groups.
Initial combination therapy with sitagliptin and metformin and monotherapy with either drug alone provided substantial and sustained glycaemic improvements and were well tolerated over 104 weeks in patients with type 2 diabetes.
评估西他列汀与二甲双胍作为初始联合治疗方案，以及在饮食和运动控制不佳的 2 型糖尿病患者（糖化血红蛋白 [HbA1c] 7.5-11%）中的单药治疗的 104 周疗效和安全性。
这是一项为期 50 周的、双盲的、随机、双盲、析因研究的 54 周扩展研究，研究初始联合应用西他列汀和二甲双胍、二甲双胍单药治疗和西他列汀单药治疗（总治疗时间 104 周）的疗效和安全性。在基础研究的 54 周中接受活性治疗的患者在扩展研究中继续接受这些治疗：西他列汀 50mg，每日两次+二甲双胍 1000mg，每日两次（高剂量联合治疗）；西他列汀 50mg，每日两次+二甲双胍 500mg，每日两次（低剂量联合治疗）；二甲双胍 1000mg，每日两次（高剂量）；二甲双胍 500mg，每日两次（低剂量）；西他列汀 100mg，每日一次。随机接受安慰剂/二甲双胍顺序治疗的患者以盲法从第 24 周开始转换为二甲双胍单药治疗，并逐渐增加剂量至 1000mg，每日两次，直至扩展研究结束。
在未开始血糖挽救治疗的进入扩展研究的患者中，从基线到第 104 周的最小二乘均数 HbA1c 变化分别为：-1.7%（高剂量联合治疗）、-1.4%（低剂量联合治疗）、-1.3%（高剂量）、-1.1%（低剂量）和-1.2%（西他列汀）。第 104 周时 HbA1c＜7%的患者比例分别为：60%（高剂量联合治疗）、45%（低剂量联合治疗）、45%（高剂量）、28%（低剂量）和 32%（西他列汀）。所有组的空腹和餐后血糖控制及胰岛β细胞功能均有改善，血糖反应在 104 周的治疗期间基本保持稳定。各组低血糖的发生率均较低。胃肠道不良反应的发生率一般在西他列汀组较低，而在二甲双胍单药治疗组和联合治疗组之间相似。
西他列汀联合二甲双胍初始治疗和单药治疗均可显著且持续改善 2 型糖尿病患者的血糖，在 104 周的治疗期间耐受性良好。
