Liraglutide effects in a paediatric (7-11y) population with obesity: A randomized, double-blind, placebo-controlled, short-term trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics
Liraglutide effects in a paediatric (7-11y) population with obesity: A randomized, double-blind, placebo-controlled, short-term trial to assess safety, tolerability, pharmacokinetics, and pharmacodynamics
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DOI：
10.1111/ijpo.12495
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发表时间：
2019-05-01
影响因子：
3.8
通讯作者：
Riesenberg, Robert A.
中科院分区：
文献类型：
--
作者：
Mastrandrea, Lucy D.;Witten, Louise;Riesenberg, Robert A.
背景儿童肥胖是一个主要的公共卫生问题，治疗选择有限。本研究的目的是评估利拉鲁肽短期治疗肥胖儿童（7- 11岁）的安全性、耐受性、药代动力学和药效学。24例儿童接受了至少一剂每日一次皮下利拉鲁肽（n=16）或安慰剂（n=8），起始剂量为0.3 mg，每周剂量递增至3.0 mg或最大耐受剂量，20名儿童完成了试验（利拉鲁肽组14名，安慰剂组6名）。主要终点是不良事件的数量。结果基线特征（平均标准差）包括以下内容：年龄9.9 +/- 1.1years，体重71.5 +/- 15.4kg，62.5%男性。9例接受利拉鲁肽治疗的受试者（56.3%）报告了37起不良事件，5例接受安慰剂治疗的受试者（62.5%）报告了12起事件。大多数不良事件的严重程度为轻度，3例为中度，无重度。胃肠道疾病是最常报告的事件，与安慰剂组（12.5%）相比，37.5%的利拉鲁肽治疗受试者发生了胃肠道疾病。5例受试者发生了6起无症状性低血糖发作，其中4例接受了利拉鲁肽治疗。利拉鲁肽暴露量与剂量比例性一致。体重是显著影响暴露量的唯一协变量。从基线到治疗结束时，体重指数（BMI）Z评分显著降低（估计治疗差异：-0.28; P=0.0062）observed.ConclusionShort-term treatment with lirin children with obesity revealed a safety and tolerance profile similar to trials in adults and adolescents with obesity，with no new safety issues.
BackgroundChildhood obesity is a major public health concern with limited treatment options.ObjectiveThe aim of this study was to assess safety, tolerability, pharmacokinetics, and pharmacodynamics during short-term treatment with liraglutide in children (7-11y) with obesity.MethodsIn this randomized, double-blind, placebo-controlled trial, 24 children received at least one dose of once-daily subcutaneous liraglutide (n=16) or placebo (n=8) starting at 0.3mg with weekly dose escalations up to 3.0mg or maximum tolerated dose, and 20 children completed the trial (14 in the liraglutide group and six in the placebo group). The primary endpoint was the number of adverse events.ResultsBaseline characteristics (meanstandard deviation) included the following: age 9.9 +/- 1.1years, weight 71.5 +/- 15.4kg, and 62.5% male. Thirty-seven adverse events were reported in nine liraglutide-treated participants (56.3%) versus 12 events in five placebo-treated participants (62.5%). Most adverse events were mild in severity, three were of moderate severity, and none were severe. Gastrointestinal disorders were the most frequently reported events occurring in 37.5% of liraglutide-treated participants compared with placebo (12.5%). Six asymptomatic hypoglycaemic episodes occurred in five participants of whom four were liraglutide treated. Liraglutide exposure was consistent with dose proportionality. Body weight was the only covariate to significantly impact exposure. A significant reduction in body mass index (BMI) Z score from baseline to end of treatment (estimated treatment difference: -0.28; P=0.0062) was observed.ConclusionShort-term treatment with liraglutide in children with obesity revealed a safety and tolerability profile similar to trials in adults and adolescents with obesity, with no new safety issues.