Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial
Effect of linagliptin monotherapy on glycaemic control and markers of β-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial
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DOI：
10.1111/j.1463-1326.2010.01350.x
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发表时间：
2011-03-01
影响因子：
5.8
通讯作者：
Dugi, K. A.
中科院分区：
文献类型：
--
作者：
Del Prato, S.;Barnett, A. H.;Dugi, K. A.
研究方法：这项多中心、随机、平行组、III期研究在2型糖尿病患者中比较了利格列汀治疗（5 mg每日一次，n = 336）与安慰剂（n = 167）24周。在随机化之前，接受一种OAD预治疗的患者经历了6周的洗脱期，其中包括最后2周的安慰剂导入期。既往未接受OAD治疗的患者接受2周安慰剂导入期。主要终点是治疗24周后HbA 1c较基线的变化。结果：利格列汀治疗导致安慰剂校正的HbA 1c较基线的变化为-0.69%（p < 0.0001）。在基线HbA 1c ≥ 9.0%的患者中，调整后的HbA 1c降低为1.01%（p < 0.0001）。与安慰剂组相比，利格列汀组患者在24周时更有可能实现HbA 1c降低≥ 0.5%（分别为47.1%和19.0%;比值比，OR = 4.2，p < 0.0001）。与安慰剂相比，利格列汀使空腹血糖改善了-1.3 mmol/l（p < 0.0001），24周后，利格列汀使餐后2小时血糖较基线校正平均降低了-3.2 mmol/l（p < 0.0001）。观察到胰岛素原/胰岛素比值（p = 0.025）、稳态模型评估-%B（p = 0.049）和处置指数（p = 0.0005）存在统计学显著性和相关治疗差异。与安慰剂相比，利格列汀组的低血糖发作没有过多，没有患者需要第三方干预。轻度或中度肾损害并不影响利格列汀的血浆谷浓度。结论：利格列汀单药治疗产生了显着的，临床意义和持续改善贫血控制，伴随着增强β细胞功能的参数。利格列汀的安全性特征与安慰剂相当。
Methods: This multicentre, randomized, parallel group, phase III study compared linagliptin treatment (5 mg once daily, n = 336) with placebo (n = 167) for 24 weeks in type 2 diabetes patients. Before randomization, patients pretreated with one OAD underwent a washout period of 6 weeks, which included a placebo run-in period during the last 2 weeks. Patients previously untreated with an OAD underwent a 2-week placebo run-in period. The primary endpoint was the change in HbA1c from baseline after 24 weeks of treatment.Results: Linagliptin treatment resulted in a placebo-corrected change in HbA1c from baseline of -0.69% (p < 0.0001) at 24 weeks. In patients with baseline HbA1c >= 9.0%, the adjusted reduction in HbA1c was 1.01% (p < 0.0001). Patients treated with linagliptin were more likely to achieve a reduction in HbA1c of >= 0.5% at 24 weeks than those in the placebo arm (47.1 and 19.0%, respectively; odds ratio, OR = 4.2, p < 0.0001). Fasting plasma glucose improved by -1.3 mmol/l (p < 0.0001) with linagliptin vs. placebo, and linagliptin produced an adjusted mean reduction from baseline after 24 weeks in 2-h postprandial glucose of -3.2 mmol/l (p < 0.0001). Statistically significant and relevant treatment differences were observed for proinsulin/insulin ratio (p = 0.025), Homeostasis Model Assessment-%B (p = 0.049) and disposition index (p = 0.0005). There was no excess of hypoglycaemic episodes with linagliptin vs. placebo and no patient required third-party intervention. Mild or moderate renal impairment did not influence the trough plasma levels of linagliptin.Conclusions: Monotherapy with linagliptin produced a significant, clinically meaningful and sustained improvement in glycaemic control, accompanied by enhanced parameters of beta-cell function. The safety profile of linagliptin was comparable with that of placebo.