美国明尼苏达大学Aaron S. Kelly小组在研究中取得进展。他们探讨了利拉鲁肽治疗青少年肥胖症的疗效。这一研究成果于2020年3月31日发表在《新英格兰医学杂志》上。

肥胖是一种慢性疾病，在儿童患者中治疗选择有限。利拉鲁肽可用于肥胖青少年的体重控制。

在这项由56周治疗+26周随访组成的随机、双盲试验中，研究组招募了肥胖且仅生活方式治疗无效的青少年（12-18岁）。除生活方式治疗外，将其按1：1随机分组，其中125例皮下注射利拉鲁肽，126例注射安慰剂。

利拉鲁肽组第56周时BMI标准偏差评分相对于基线的变化优于安慰剂组。利拉鲁肽组和安慰剂组中分别有43.3%和18.7%的参与者BMI至少降低了5%，26.1%和8.1%的参与者BMI至少降低了10%。与安慰剂组相比，利拉鲁肽组的BMI和体重降低幅度更大。

停药后，与安慰剂组相比，利拉鲁肽组的BMI标准偏差评分增加幅度更大。利拉鲁肽组中胃肠道不良反应的发生率为64.8%，显著高于安慰剂组（36.5%）；利拉鲁肽组有10.4%的患者因不良反应而停药，安慰剂组无人停药。两组中严重不良事件的发生率分别为2.4%和4.0%。利拉鲁肽组中有1例患者自杀，但研究者评估不太可能与试验治疗有关。

总之，对于青少年肥胖症，在生活方式治疗的基础上，利拉鲁肽与安慰剂相比，可显著降低患者的BMI标准偏差评分。

附：英文原文

Title: A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity | NEJM

Author: Aaron S. Kelly, Ph.D.,, Pernille Auerbach, M.D., Ph.D.,, Margarita Barrientos-Perez, M.D.,, Inge Gies, M.D., Ph.D.,, Paula M. Hale, M.D.,, Claude Marcus, M.D., Ph.D.,, Lucy D. Mastrandrea, M.D., Ph.D.,, Nandana Prabhu, M.Sc.,, and Silva Arslanian, M.D.

Issue&Volume: 2020-03-31

Abstract: Abstract

Background

Obesity is a chronic disease with limited treatment options in pediatric patients. Liraglutide may be useful for weight management in adolescents with obesity.

Methods

In this randomized, double-blind trial, which consisted of a 56-week treatment period and a 26-week follow-up period, we enrolled adolescents (12 to <18 years of age) with obesity and a poor response to lifestyle therapy alone. Participants were randomly assigned (1:1) to receive either liraglutide (3.0 mg) or placebo subcutaneously once daily, in addition to lifestyle therapy. The primary end point was the change from baseline in the body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) standard-deviation score at week 56.

Results

A total of 125 participants were assigned to the liraglutide group and 126 to the placebo group. Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, 0.22; 95% confidence interval [CI], 0.37 to 0.08; P=0.002). A reduction in BMI of at least 5% was observed in 51 of 113 participants in the liraglutide group and in 20 of 105 participants in the placebo group (estimated percentage, 43.3% vs. 18.7%), and a reduction in BMI of at least 10% was observed in 33 and 9, respectively (estimated percentage, 26.1% vs. 8.1%). A greater reduction was observed with liraglutide than with placebo for BMI (estimated difference, 4.64 percentage points) and for body weight (estimated difference, 4.50 kg [for absolute change] and 5.01 percentage points [for relative change]). After discontinuation, a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (estimated difference, 0.15; 95% CI, 0.07 to 0.23). More participants in the liraglutide group than in the placebo group had gastrointestinal adverse events (81 of 125 [64.8%] vs. 46 of 126 [36.5%]) and adverse events that led to discontinuation of the trial treatment (13 [10.4%] vs. 0). Few participants in either group had serious adverse events (3 [2.4%] vs. 5 [4.0%]). One suicide, which occurred in the liraglutide group, was assessed by the investigator as unlikely to be related to the trial treatment.

Conclusions

In adolescents with obesity, the use of liraglutide (3.0 mg) plus lifestyle therapy led to a significantly greater reduction in the BMI standard-deviation score than placebo plus lifestyle therapy.

DOI: 10.1056/NEJMoa1916038

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1916038