Once-Weekly Semaglutide in Adolescents with Obesity.
Once-Weekly Semaglutide in Adolescents with Obesity.
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DOI：
10.1056/nejmoa2208601
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发表时间：
2022-12-15
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每周一次、2.4 mg剂量的皮下注射索马鲁肽（一种胰高血糖素样肽-1受体激动剂）用于治疗成人肥胖，但目前缺乏对该药物在青少年中的评估。在这项双盲、平行组、随机、安慰剂对照试验中，我们招募了肥胖（体重指数[BMI]在第95百分位数或更高）或超重（BMI在第85百分位数或更高）且至少有一种体重相关共存疾病的青少年（12至<18岁）。受试者以2：1的比例随机分配接受每周一次皮下semaglutide（剂量为2.4 mg）或安慰剂治疗68周，外加生活方式干预。主要终点是BMI从基线到第68周的百分比变化;次要确证性终点是第68周时体重减轻至少5%。共有201名参与者接受了随机分组，180名（90%）完成了治疗。除一人外，所有参与者都有肥胖症。Semaglutide组从基线至第68周BMI的平均变化为−16.1%，安慰剂组为0.6%（估计差异，−16.7个百分点; 95%置信区间[CI]，−20.3至−13.2; P<0.001）。第68周时，Semaglutide组131例受试者中共有95例（73%）体重减轻5%或以上，而安慰剂组62例受试者中有11例（18%）体重减轻（估计比值比，14.0; 95% CI，6.3 - 31.0; P<0.001）。Semaglutide组的体重减轻和心脏代谢风险因素（腰围和糖化血红蛋白、脂质[高密度脂蛋白胆固醇除外]和丙氨酸转氨酶水平）的改善大于安慰剂组。Semaglutide组胃肠道不良事件的发生率高于安慰剂组（62% vs. 42%）。Semaglutide组5例受试者（4%）和安慰剂组0例受试者发生胆石症。Semaglutide组15/133例受试者（11%）和安慰剂组6/67例受试者（9%）报告了严重不良事件。在肥胖青少年中，每周一次2.4 mg剂量semaglutide治疗加生活方式干预导致的BMI降低幅度大于单独生活方式干预。（由诺和诺德资助; STEP TEENS ClinicalTrials.gov编号，NCT 04102189。）
A once-weekly, 2.4-mg dose of subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, is used to treat obesity in adults, but assessment of the drug in adolescents has been lacking. In this double-blind, parallel-group, randomized, placebo-controlled trial, we enrolled adolescents (12 to <18 years of age) with obesity (a body-mass index [BMI] in the 95th percentile or higher) or with overweight (a BMI in the 85th percentile or higher) and at least one weight-related coexisting condition. Participants were randomly assigned in a 2:1 ratio to receive once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo for 68 weeks, plus lifestyle intervention. The primary end point was the percentage change in BMI from baseline to week 68; the secondary confirmatory end point was weight loss of at least 5% at week 68. A total of 201 participants underwent randomization, and 180 (90%) completed treatment. All but one of the participants had obesity. The mean change in BMI from baseline to week 68 was −16.1% with semaglutide and 0.6% with placebo (estimated difference, −16.7 percentage points; 95% confidence interval [CI], −20.3 to −13.2; P<0.001). At week 68, a total of 95 of 131 participants (73%) in the semaglutide group had weight loss of 5% or more, as compared with 11 of 62 participants (18%) in the placebo group (estimated odds ratio, 14.0; 95% CI, 6.3 to 31.0; P<0.001). Reductions in body weight and improvement with respect to cardiometabolic risk factors (waist circumference and levels of glycated hemoglobin, lipids [except high-density lipoprotein cholesterol], and alanine aminotransferase) were greater with semaglutide than with placebo. The incidence of gastrointestinal adverse events was greater with semaglutide than with placebo (62% vs. 42%). Five participants (4%) in the semaglutide group and no participants in the placebo group had cholelithiasis. Serious adverse events were reported in 15 of 133 participants (11%) in the semaglutide group and in 6 of 67 participants (9%) in the placebo group. Among adolescents with obesity, once-weekly treatment with a 2.4-mg dose of semaglutide plus lifestyle intervention resulted in a greater reduction in BMI than lifestyle intervention alone. (Funded by Novo Nordisk; STEP TEENS ClinicalTrials.gov number, NCT04102189.)