Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study
Safety and efficacy of linagliptin as add-on therapy to metformin in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study
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DOI：
10.1111/j.1463-1326.2010.01326.x
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发表时间：
2011-01-01
影响因子：
5.8
通讯作者：
Woerle, H. -J.
中科院分区：
文献类型：
--
作者：
Taskinen, M. -R.;Rosenstock, J.;Woerle, H. -J.
目的：评价强效选择性二肽基肽酶-4 （DPP-4）抑制剂利格列汀作为二甲双胍辅助治疗血糖控制不佳的2型糖尿病患者的疗效和安全性。方法：这项为期24周的随机、安慰剂对照、双盲、平行组研究在10个国家的82个中心进行。HbA1c水平为7.0-10.0%的患者，在筛查时停止服用二甲双胍和最多一种额外的抗糖尿病药物，继续服用二甲双胍>= 1500mg /天，持续6周，包括2周的安慰剂适应期，然后随机分配到利格列汀5mg每日一次（n = 524）或安慰剂（n = 177）。主要终点是治疗24周后HbA1c较基线的变化，用协方差分析（ANCOVA）进行评估。结果：平均基线HbA1c和空腹血糖（FPG）分别为8.1%和9.4 mmol/l。与安慰剂相比，利格列汀在调整后的HbA1c （-0.49 vs. 0.15%）、FPG （-0.59 vs. 0.58 mmol/l）和2hPPG （-2.7 vs. 1.0 mmol/l）的基线平均变化显著降低；p < 0.0001。低血糖很少见，利格列汀组有3例（0.6%）低血糖，安慰剂组有5例（2.8%）低血糖。两组的体重与基线相比没有显著变化（安慰剂-0.5 kg，利格列汀-0.4 kg）。结论：在二甲双胍控制不充分的2型糖尿病患者中，每日1次加用利格列汀5mg可显著改善血糖控制，且无体重增加或低血糖风险增加。
Aim: To evaluate the efficacy and safety of the potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin administered as add-on therapy to metformin in patients with type 2 diabetes with inadequate glycaemic control.Methods: This 24-week, randomized, placebo-controlled, double-blind, parallel-group study was carried out in 82 centres in 10 countries. Patients with HbA1c levels of 7.0-10.0% on metformin and a maximum of one additional antidiabetes medication, which was discontinued at screening, continued on metformin >= 1500 mg/day for 6 weeks, including a placebo run-in period of 2 weeks, before being randomized to linagliptin 5 mg once daily (n = 524) or placebo (n = 177) add-on. The primary outcome was the change from baseline in HbA1c after 24 weeks of treatment, evaluated with an analysis of covariance (ANCOVA).Results: Mean baseline HbA1c and fasting plasma glucose (FPG) were 8.1% and 9.4 mmol/l, respectively. Linagliptin showed significant reductions vs. placebo in adjusted mean changes from baseline of HbA1c (-0.49 vs. 0.15%), FPG (-0.59 vs. 0.58 mmol/l) and 2hPPG (-2.7 vs. 1.0 mmol/l); all p < 0.0001. Hypoglycaemia was rare, occurring in three patients (0.6%) treated with linagliptin and five patients (2.8%) in the placebo group. Body weight did not change significantly from baseline in both groups (-0.5 kg placebo, -0.4 kg linagliptin).Conclusions: The addition of linagliptin 5 mg once daily in patients with type 2 diabetes inadequately controlled on metformin resulted in a significant and clinically meaningful improvement in glycaemic control without weight gain or increased risk of hypoglycaemia.