利拉鲁肽治疗肥胖青少年的随机对照试验。

A Randomized, Controlled Trial of Liraglutide for Adolescents with Obesity.

机构信息

From the Department of Pediatrics and Center for Pediatric Obesity Medicine, University of Minnesota Medical School, Minneapolis (A.S.K.); Novo Nordisk, Søborg, Denmark (P.A.); Pediatric Endocrinology, Hospital Ángeles Puebla, Puebla City, Mexico (M.B.-P.); the Department of Pediatrics, Division of Pediatric Endocrinology, Universitair Ziekenhuis Brussel, Brussels (I.G.); Novo Nordisk, Plainsboro, NJ (P.M.H.); the Division of Pediatrics, Department of Clinical Science Intervention and Technology, Karolinska Institutet, Stockholm (C.M.); the Division of Pediatric Endocrinology and Diabetes, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY (L.D.M.); Novo Nordisk, Bengaluru, India (N.P.); and the Center for Pediatric Research in Obesity and Metabolism, Division of Pediatric Endocrinology, Metabolism, and Diabetes Mellitus, University of Pittsburgh Medical Center Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh (S.A.).

出版信息

N Engl J Med. 2020 May 28;382(22):2117-2128. doi: 10.1056/NEJMoa1916038. Epub 2020 Mar 31.

DOI:10.1056/NEJMoa1916038

PMID:32233338

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. (Funded by Novo Nordisk; NN8022-4180 ClinicalTrials.gov number, NCT02918279.).

摘要

背景

肥胖是一种慢性疾病，儿科患者的治疗选择有限。利拉鲁肽可能对肥胖青少年的体重管理有用。

方法

在这项随机、双盲试验中，包括 56 周的治疗期和 26 周的随访期，我们招募了肥胖且对单独生活方式治疗反应不佳的青少年（12 至<18 岁）。参与者被随机分配（1:1）接受利拉鲁肽（3.0mg）或安慰剂皮下注射，每天一次，同时接受生活方式治疗。主要终点是第 56 周时体重指数（BMI；体重以千克为单位除以身高以米为单位的平方）标准差评分的基线变化。

结果

共有 125 名参与者被分配到利拉鲁肽组，126 名参与者被分配到安慰剂组。与安慰剂相比，利拉鲁肽在第 56 周时 BMI 标准差评分的变化更大（估计差值，-0.22；95%置信区间[CI]，-0.37 至-0.08；P=0.002）。利拉鲁肽组有 113 名参与者中的 51 名（43.3%）和安慰剂组有 105 名参与者中的 20 名（18.7%）的 BMI 至少降低了 5%，利拉鲁肽组有 33 名（26.1%）和安慰剂组有 9 名（8.1%）的 BMI 至少降低了 10%。与安慰剂相比，利拉鲁肽对 BMI（估计差值，-4.64 个百分点）和体重（估计差值，-4.50 公斤[绝对变化]和-5.01 个百分点[相对变化]）的降低更为明显。停止治疗后，与安慰剂相比，利拉鲁肽组 BMI 标准差评分的增加更为明显（估计差值，0.15；95%CI，0.07 至 0.23）。与安慰剂组相比，利拉鲁肽组更多的参与者出现胃肠道不良事件（125 名中的 81 名[64.8%]与 126 名中的 46 名[36.5%]）和导致试验治疗停止的不良事件（13 名[10.4%]与 0 名）。两组中很少有参与者发生严重不良事件（3 名[2.4%]与 5 名[4.0%]）。利拉鲁肽组发生的一起自杀事件被研究者评估为不太可能与试验治疗有关。