Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study
Initial combination of linagliptin and metformin improves glycaemic control in type 2 diabetes: a randomized, double-blind, placebo-controlled study
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DOI：
10.1111/j.1463-1326.2012.01590.x
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发表时间：
2012-06-01
影响因子：
5.8
通讯作者：
Woerle, H. -J.
中科院分区：
文献类型：
--
作者：
Haak, T.;Meinicke, T.;Woerle, H. -J.
目的：评价利格列汀+二甲双胍初始联合治疗与利格列汀或二甲双胍单药治疗在2型糖尿病患者中的疗效和安全性。方法：在这项为期24周、双盲、安慰剂对照的III期试验中，791名患者被随机分配到6个治疗组中的一个。两个自由联合治疗组接受利格列汀2.5 mg每日两次（bid）+低剂量（500 mg）或高剂量（1000 mg）二甲双胍bid。4个单药治疗组接受利格列汀5 mg每日一次、二甲双胍500 mg或1000 mg bid或安慰剂。血红蛋白A1 c（HbA 1c）≥ 11.0%的患者不符合随机化条件，接受开放标签利格列汀+高剂量二甲双胍治疗。结果如下：安慰剂校正均值HbA 1c较基线的变化（95%置信区间）（8.7%）至第24周为-1.7%（-2.0，-1.4）利格列汀+高剂量二甲双胍，-1.3%（-1.6，-1.1）利格列汀+低剂量二甲双胍，-1.2%（-1.5，-0.9），低剂量二甲双胍为-0.8%（-1.0，-0.5），利格列汀为-0.6（-0.9，-0.3）（均p < 0.0001）。在开放标签组中，HbA 1c较基线的平均变化（11.8%）为-3.7%。利格列汀+二甲双胍组（1.7%）低血糖发生率与二甲双胍单药组（2.4%）相似。各治疗组的不良事件发生率相当。未观察到体重发生具有临床意义的变化。结论：在改善血糖控制方面，利格列汀+二甲双胍初始联合治疗上级二甲双胍单药治疗，安全性和耐受性特征相似，无体重增加，低血糖风险低。
Aims: To evaluate the efficacy and safety of initial combination therapy with linagliptin plus metformin versus linagliptin or metformin monotherapy in patients with type 2 diabetes. Methods: In this 24-week, double-blind, placebo-controlled, Phase III trial, 791 patients were randomized to one of six treatment arms. Two free combination therapy arms received linagliptin 2.5 mg twice daily (bid) + either low (500 mg) or high (1000 mg) dose metformin bid. Four monotherapy arms received linagliptin 5 mg once daily, metformin 500 mg or 1000 mg bid or placebo. Patients with haemoglobin A1c (HbA1c) = 11.0% were not eligible for randomization and received open-label linagliptin + high-dose metformin. Results: The placebo-corrected mean (95% confidence interval) change in HbA1c from baseline (8.7%) to week 24 was -1.7% (-2.0, -1.4) for linagliptin + high-dose metformin, -1.3% (-1.6, -1.1) for linagliptin + low-dose metformin, -1.2% (-1.5, -0.9) for high-dose metformin, -0.8% (-1.0, -0.5) for low-dose metformin and -0.6 (-0.9, -0.3) for linagliptin (all p < 0.0001). In the open-label arm, the mean change in HbA1c from baseline (11.8%) was -3.7%. Hypoglycaemia occurred at a similar low rate with linagliptin + metformin (1.7%) as with metformin alone (2.4%). Adverse event rates were comparable across treatment arms. No clinically significant changes in body weight were noted. Conclusions: Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control, with a similar safety and tolerability profile, no weight gain and a low risk of hypoglycaemia.