Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial.
Effect of liraglutide 3.0 mg in individuals with obesity and moderate or severe obstructive sleep apnea: the SCALE Sleep Apnea randomized clinical trial.
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DOI：
10.1038/ijo.2016.52
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发表时间：
2016-08
期刊：
影响因子：
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通讯作者：
Mignot E
中科院分区：
文献类型：
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作者：
Blackman A;Foster GD;Zammit G;Rosenberg R;Aronne L;Wadden T;Claudius B;Jensen CB;Mignot E
肥胖与阻塞性睡眠呼吸暂停（OSA）的患病率密切相关，减肥已被证明可以降低疾病的严重程度。以32周后呼吸暂停低通气指数（AHI）变化为主要终点，研究利拉鲁肽3.0 mg与安慰剂相比是否能降低OSA严重程度。利拉鲁肽的减肥效果也进行了研究。在这个随机的双盲试验中，患有中度（AHI 15-29.9事件h−1）或严重（AHI大于或等于30事件h−1）OSA并且不愿意/不能使用持续气道正压治疗的肥胖非糖尿病参与者被随机分配到利拉鲁肽3.0 mg （n=180）或安慰剂（n=179），为期32周，作为饮食（500千卡每日不足）和运动的辅助。各组基线特征相似（平均年龄48.5岁，男性71.9%,AHI 49.2事件h−1，重度OSA 67.1%，体重117.6 kg，体重指数39.1 kg m−2，糖尿病前期63.2%,HbA1c 5.7%）。32周后，利拉鲁肽组AHI的平均降幅大于安慰剂组（- 12.2 vs - 6.1事件h−1，估计治疗差异：- 6.1事件h−1(95%可信区间（CI）， - 11.0至- 1.2)，P=0.0150）。与安慰剂相比，利拉鲁肽产生了更大的平均体重减轻百分比（- 5.7% vs - 1.6%，估计治疗差异：- 4.2% (95% CI, - 5.2至- 3.1%)，P<0.0001）。事后证实体重减轻程度与OSA终点改善之间有统计学意义的关联（P<0.01）。利拉鲁肽组与安慰剂组相比，糖化血红蛋白（HbA1c）和收缩压（SBP）的降低幅度更大（P<0.001）。利拉鲁肽3.0 mg的安全性与剂量≥1.8 mg的安全性相似。作为饮食和运动的辅助，利拉鲁肽3.0 mg通常耐受性良好，在肥胖和中/重度OSA患者中，其AHI、体重、收缩压和HbA1c的降低明显大于安慰剂。结果证实，减肥改善了osa相关参数。
Obesity is strongly associated with prevalence of obstructive sleep apnea (OSA), and weight loss has been shown to reduce disease severity. To investigate whether liraglutide 3.0 mg reduces OSA severity compared with placebo using the primary end point of change in apnea–hypopnea index (AHI) after 32 weeks. Liraglutide's weight loss efficacy was also examined. In this randomized, double-blind trial, non-diabetic participants with obesity who had moderate (AHI 15–29.9 events h−1) or severe (AHI ⩾30 events h−1) OSA and were unwilling/unable to use continuous positive airway pressure therapy were randomized for 32 weeks to liraglutide 3.0 mg (n=180) or placebo (n=179), both as adjunct to diet (500 kcal day−1 deficit) and exercise. Baseline characteristics were similar between groups (mean age 48.5 years, males 71.9%, AHI 49.2 events h−1, severe OSA 67.1%, body weight 117.6 kg, body mass index 39.1 kg m−2, prediabetes 63.2%, HbA1c 5.7%). After 32 weeks, the mean reduction in AHI was greater with liraglutide than with placebo (−12.2 vs −6.1 events h−1, estimated treatment difference: −6.1 events h−1 (95% confidence interval (CI), −11.0 to −1.2), P=0.0150). Liraglutide produced greater mean percentage weight loss compared with placebo (−5.7% vs −1.6%, estimated treatment difference: −4.2% (95% CI, −5.2 to −3.1%), P<0.0001). A statistically significant association between the degree of weight loss and improvement in OSA end points (P<0.01, all) was demonstrated post hoc. Greater reductions in glycated hemoglobin (HbA1c) and systolic blood pressure (SBP) were seen with liraglutide versus placebo (both P<0.001). The safety profile of liraglutide 3.0 mg was similar to that seen with doses ⩽1.8 mg. As an adjunct to diet and exercise, liraglutide 3.0 mg was generally well tolerated and produced significantly greater reductions than placebo in AHI, body weight, SBP and HbA1c in participants with obesity and moderate/severe OSA. The results confirm that weight loss improves OSA-related parameters.