Diabetes Research Division, Department of Internal Medicine F, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
Diabetes Obes Metab. 2010 Feb;12(2):167-77. doi: 10.1111/j.1463-1326.2009.01173.x.
To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes.
After a 2 week placebo run-in period, eligible patients inadequately controlled on long-acting, intermediate-acting or premixed insulin (HbA1c > or = 7.5% and < or = 11%), were randomised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period. The study capped the proportion of randomised patients on insulin plus metformin at 75%. Further, the study capped the proportion of randomised patients on premixed insulin at 25%. The metformin dose and the insulin dose were to remain stable throughout the study. The primary endpoint was HbA1c change from baseline at week 24.
Mean baseline characteristics were similar between the sitagliptin (n = 322) and placebo (n = 319) groups, including HbA1c (8.7 vs. 8.6%), diabetes duration (13 vs. 12 years), body mass index (31.4 vs. 31.4 kg/m(2)), and total daily insulin dose (51 vs. 52 IU), respectively. At 24 weeks, the addition of sitagliptin significantly (p < 0.001) reduced HbA1c by 0.6% compared with placebo (0.0%). A greater proportion of patients achieved an HbA1c level < 7% while randomised to sitagliptin as compared with placebo (13 vs. 5% respectively; p < 0.001). Similar HbA1c reductions were observed in the patient strata defined by insulin type (long-acting and intermediate-acting insulins or premixed insulins) and by baseline metformin treatment. The addition of sitagliptin significantly (p < 0.001) reduced fasting plasma glucose by 15.0 mg/dl (0.8 mmol/l) and 2-h postmeal glucose by 36.1 mg/dl (2.0 mmol/l) relative to placebo. A higher incidence of adverse experiences was reported with sitagliptin (52%) compared with placebo (43%), due mainly to the increased incidence of hypoglycaemia (sitagliptin, 16% vs. placebo, 8%). The number of hypoglycaemic events meeting the protocol-specified criteria for severity was low with sitagliptin (n = 2) and placebo (n = 1). No significant change from baseline in body weight was observed in either group.
In this 24-week study, the addition of sitagliptin to ongoing, stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes.
评估西他列汀在单独使用胰岛素或与二甲双胍联合治疗 2 型糖尿病患者中的疗效和耐受性。
在为期 2 周的安慰剂导入期后，未能充分控制的长作用、中作用或预混胰岛素（HbA1c > 7.5%且 < 11%）的合格患者被随机分配至每日一次西他列汀 100mg 或匹配安慰剂组，持续 24 周。研究将随机分配的胰岛素加二甲双胍患者比例限制在 75%。此外，研究将随机分配的预混胰岛素患者比例限制在 25%。整个研究过程中，二甲双胍剂量和胰岛素剂量保持稳定。主要终点是第 24 周时的 HbA1c 与基线相比的变化。
西他列汀（n = 322）和安慰剂（n = 319）组的平均基线特征相似，包括 HbA1c（8.7%比 8.6%）、糖尿病病程（13 年比 12 年）、体重指数（31.4kg/m2 比 31.4kg/m2）和总日胰岛素剂量（51IU 比 52IU）。24 周时，与安慰剂相比，西他列汀（p < 0.001）显著降低了 0.6%的 HbA1c（0.0%）。与安慰剂相比，更多的患者在随机接受西他列汀治疗时达到了 HbA1c < 7%的水平（分别为 13%比 5%；p < 0.001）。在按胰岛素类型（长效和中效胰岛素或预混胰岛素）和基线时接受二甲双胍治疗的患者亚组中，也观察到类似的 HbA1c 降低。与安慰剂相比，西他列汀（p < 0.001）显著降低了 15.0mg/dl（0.8mmol/l）的空腹血糖和 36.1mg/dl（2.0mmol/l）的餐后 2 小时血糖。与安慰剂相比，西他列汀的不良事件发生率更高（52%比 43%），主要是由于低血糖的发生率增加（西他列汀 16%比安慰剂 8%）。西他列汀（n = 2）和安慰剂（n = 1）发生符合方案规定严重程度标准的低血糖事件的数量较低。两组体重均无明显变化。
在这项为期 24 周的研究中，与持续稳定剂量的胰岛素治疗联合或不联合二甲双胍相比，西他列汀的添加改善了血糖控制，并且在 2 型糖尿病患者中通常具有良好的耐受性。
