新英格兰:健康减肥的临床试验新消息来啦

背景:


随着生活水平的提高,当前社会肥胖率正在不断增加。肥胖者体内脂肪过多、缺乏身体锻炼,这会损害健康并增加死亡风险。曾有研究显示,体重减轻3%至5%可以减少肥胖相关危险因素。对于并存疾病,病态肥胖或两者兼有的患者,建议减轻超过初始体重的5%-15%。许多患者最初体重大幅减轻后如果不遵循结构化的体重维持计划,通常会体重反弹。有计划的有氧运动能增加能量消耗,锻炼心肺功能,同时减少脂肪量并保持或增加肌肉量。饮食管理计划,包括使用低热量膳食替代产品,可以维持低热量饮食引起的体重减轻,使体重反弹减轻。此外,鼓励增加体育锻炼同时限制卡路里的生活方式干预已被证明可以维持适度的体重减轻。然而,运动对于防止体重减轻后体重反弹的单独益处尚未得到充分研究。


利拉鲁肽是一种胰高血糖素样肽-1(GLP-1)受体激动剂,用于治疗肥胖症。它可以诱导体重减轻,并通过抑制食欲的方式使低卡路里饮食诱导的体重减轻至少维持1年。之前的研究中,运动,药物或组合策略是否构成维持健康体重减轻的更有效方法仍然是一个悬而未决的问题。


2021年5月6日,Julie R. Lundgren等研究者在《新英格兰医学杂志》上发表了一项临床研究的结果,该研究评估了与安慰剂相比,中度至剧烈运动计划,每天3.0mg剂量的利拉鲁肽或运动加利拉鲁肽组合治疗1年对低热量饮食体重减轻后健康体重减轻的维持效果。


方法:


在一项随机,头对头,安慰剂对照试验中,研究者们招募了未患糖尿病的肥胖成年人(体重指数[体重公斤除以身高米的平方],32-43)。经过8周的低热量饮食后,参与者被随机分配到以下四种策略中的一种:中等到高强度的运动计划加安慰剂(运动组);用利拉鲁肽(3.0mg/天)加常规活动治疗(利拉鲁肽组);运动项目加利拉鲁肽治疗(联合组);或安慰剂加常规活动(安慰剂组)。预先假设的终点是从随机分组到治疗期结束的意向治疗人群的体重变化(主要终点)和体脂百分比变化(次要终点)。同时还评估了与代谢相关的预定终点和安全性。


结果:


8周低热量饮食后,195名参与者的体重平均下降13.1公斤。在1年后,与安慰剂组相比,所有积极的治疗策略组的体重都减轻得更多:运动组的差异为-4.1kg(95%置信区间[CI],-7.8至-0.4;P=0.03);利拉鲁肽组为-6.8kg(95%CI,-10.4至-3.1;P<0.001);联合用药组为-9.5 kg(95%CI,-13.1至-5.9;P<0.001)。联合治疗导致的体重减轻效果比运动更好(-5.4公斤;95%CI,-9.0至-1.7;P=0.004),利拉鲁肽组的体重减轻效果也比运动组好(-2.7公斤;95%CI,-6.3至0.8;P=0.13)。联合治疗使体脂百分比下降3.9个百分点,约为运动组和利拉鲁肽组下降的两倍(运动组:-1.7个百分点;95%CI,-3.2至-0.2;P=0.02。利拉鲁肽组:-1.9个百分点;95%CI,-3.3至-0.5;P=0.009)。只有联合治疗能改善糖化血红蛋白水平,胰岛素敏感性和心肺功能。利拉鲁肽组的心率增加和胆石症发生率高于联合治疗组。


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实验期间各组体重和体脂百分比的变化


结论:


运动和利拉鲁肽治疗相结合的策略比单独治疗改善健康减肥维持的效果更好。


原文摘要:


Background: 


Weight regain after weight loss is a major problem in the treatment of persons with obesity.


Methods: 


In a randomized, head-to-head, placebo-controlled trial, we enrolled adults with obesity (body-mass index [the weight in kilograms divided by the square of the height in meters], 32 to 43) who did not have diabetes. After an 8-week low-calorie diet, participants were randomly assigned for 1 year to one of four strategies: a moderate-to-vigorous-intensity exercise program plus placebo (exercise group); treatment with liraglutide (3.0 mg per day) plus usual activity (liraglutide group); exercise program plus liraglutide therapy (combination group); or placebo plus usual activity (placebo group). End points with prespecified hypotheses were the change in body weight (primary end point) and the change in body-fat percentage (secondary end point) from randomization to the end of the treatment period in the intention-to-treat population. Prespecified metabolic health-related end points and safety were also assessed.


Results: 


After the 8-week low-calorie diet, 195 participants had a mean decrease in body weight of 13.1 kg. At 1 year, all the active-treatment strategies led to greater weight loss than placebo: difference in the exercise group, -4.1 kg (95% confidence interval [CI], -7.8 to -0.4; P = 0.03); in the liraglutide group, -6.8 kg (95% CI, -10.4 to -3.1; P<0.001); and in the combination group, -9.5 kg (95% CI, -13.1 to -5.9; P<0.001). The combination strategy led to greater weight loss than exercise (difference, -5.4 kg; 95% CI, -9.0 to -1.7; P = 0.004) but not liraglutide (-2.7 kg; 95% CI, -6.3 to 0.8; P = 0.13). The combination strategy decreased body-fat percentage by 3.9 percentage points, which was approximately twice the decrease in the exercise group (-1.7 percentage points; 95% CI, -3.2 to -0.2; P = 0.02) and the liraglutide group (-1.9 percentage points; 95% CI, -3.3 to -0.5; P = 0.009). Only the combination strategy was associated with improvements in the glycated hemoglobin level, insulin sensitivity, and cardiorespiratory fitness. Increased heart rate and cholelithiasis were observed more often in the liraglutide group than in the combination group.


Conclusions: 


A strategy combining exercise and liraglutide therapy improved healthy weight loss maintenance more than either treatment alone. (Funded by the Novo Nordisk Foundation and others; EudraCT number, 2015-005585-32; ClinicalTrials.gov number, NCT04122716.).


参考文献:


Lundgren, J.R., et al., Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med, 2021. 384(18): p. 1719-1730



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