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利拉利汀对早期 2 型糖尿病患者脉搏波速度的影响:一项随机、双盲、对照的 26 周试验(RELEASE)。

Effect of linagliptin on pulse wave velocity in early type 2 diabetes: A randomized, double-blind, controlled 26-week trial (RELEASE).

机构信息

Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.

出版信息

Diabetes Obes Metab. 2017 Aug;19(8):1147-1154. doi: 10.1111/dom.12925. Epub 2017 Apr 10.

Abstract

AIMS

To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes.

METHODS

A total of 45 people with type 2 diabetes (median [interquartile range] age 63 [54-66] years, 61% men, mean ± standard deviation glycated haemoglobin [HbA1c] 6.3% ± 0.4% [45 ± 4.6 mmol/mol]), without cardiovascular disease and naïve to antidiabetic treatment, were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4 and 26 weeks of treatment, and again at 30, 4 weeks after treatment. The primary endpoint was between-group difference in PWV (corrected for systolic blood pressure [SBP]) at week 26. Secondary endpoints included differences in central SBP and augmentation index (AIx).

RESULTS

Compared with placebo, 26 weeks of linagliptin decreased PWV by an average of 0.91 m/s (95% confidence interval -1.76 to -0.06; P = .035). PWV returned to baseline after 4 weeks washout. Differences in central SBP and AIx were not different between linagliptin and placebo. Linagliptin decreased HbA1c (-0.4%; P < .001), fasting plasma glucose (-0.7 mmol/L; P = .002) and triglycerides (-0.49 mmol/L; P = .019) as compared with placebo. The changes in body weight, cholesterol and high-sensitivity C-reactive protein did not differ between groups.

CONCLUSIONS

Linagliptin decreased aortic PWV in people with early-stage type 2 diabetes as compared with placebo after 26 weeks of treatment. These results suggest that linagliptin has a favourable effect on arterial stiffness.

摘要

目的

评估二肽基肽酶-4(DPP-4)抑制剂利拉利汀对脉波速度(PWV)的影响,PWV 是动脉僵硬度和早期动脉粥样硬化的替代标志物,研究对象为早期 2 型糖尿病患者。

方法

共纳入 45 名 2 型糖尿病患者(中位数[四分位数间距]年龄 63 [54-66]岁,61%为男性,平均[±]标准差糖化血红蛋白[HbA1c]6.3%[45±4.6]mmol/mol]),无心血管疾病且未接受过降糖治疗,他们被随机(1:1)分为利拉利汀 5mg 每日一次或安慰剂组,进行为期 26 周的双盲治疗。在基线、治疗 4 周和 26 周时评估 PWV,并在治疗结束后 30 周和 4 周时再次评估。主要终点是治疗 26 周时 PWV(校正收缩压[SBP])的组间差异。次要终点包括中心 SBP 和增强指数(AIx)的差异。

结果

与安慰剂相比,26 周的利拉利汀治疗使 PWV 平均降低 0.91m/s(95%置信区间-1.76 至-0.06;P=0.035)。停药 4 周后,PWV 恢复至基线水平。利拉利汀与安慰剂相比,中心 SBP 和 AIx 差异无统计学意义。与安慰剂相比,利拉利汀降低了 HbA1c(-0.4%;P<0.001)、空腹血糖(-0.7mmol/L;P=0.002)和甘油三酯(-0.49mmol/L;P=0.019)。体重、胆固醇和高敏 C 反应蛋白的变化两组间无差异。

结论

与安慰剂相比,26 周的利拉利汀治疗可降低早期 2 型糖尿病患者的主动脉 PWV。这些结果表明,利拉利汀对动脉僵硬度有有利影响。

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