作者：
Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J.
作者单位：
Chanoine JP, 医学博士: 加拿大温哥华哥伦比亚儿童医院内分泌和糖尿病科；
Hampl S, 医学博士: 美国密苏里州·堪萨斯城·儿童慈爱医院；
Jensen C, 医学博士: 美国德克萨斯州·休斯敦·贝勒医学院医学系；;
Boldrin M,硕士, Hauptman,医学博士: 美国新泽西州罗氏制药公司.
【摘自】美国医学协会杂志 2005年第293期: 2873-83
【摘要】
背景：儿童和青少年超重和肥胖的患病率正在迅速增长。在这些人口中，单一的行为疗法在提供意义的、持续的减重方面具有其局限性，其次，药物治疗没有被广泛的研究。
目地：确认奥利司他对肥胖青少年的有效性和安全性。
设计、设置和患者：持续54周的多中心、随机、双盲试验，研究539名肥胖青少年(12—16岁，BMI≥30)，研究在位于美国和加拿大的32个医疗中心展开。
干预：在539名的受试者中，357名受试者接受持续一年的奥利司他治疗(120mg，每日三次)，其余182名则接受安慰剂治疗，同时两组均接受温和的低热量饮食(脂肪含量为30%)，锻炼和行为干预。
主要观察指标：BMI的变化；腰和臀围的变化、体重减轻、脂肪含量测量，口服葡萄糖对血糖和血脂的影响等；
结果：到第12周时两组的BMI水平均有所下降。之后奥利司他组保持稳定，但安慰剂组则超过基线增长。在研究尾期，奥利司他组的BMI降低了0.55，而安慰剂组则增加了0.31。奥利司他组中有26.5%的受试者减少了5%以上的BMI，而安慰剂组只有15.7%。奥利司他组中有13.3%的受试者减少了约10%以上的BMI，而安慰剂组只有4.5%。研究结束后，奥利司他组的体重增长了0.53kg，安慰剂组增长了3.14kg。双能x射线吸收仪表示这种差异主要是在于脂肪含量的变化。奥利司他组中腰围减少了1.33cm，而安慰剂组中则增长了0.12cm。奥利司他组中轻度的胃肠道反应发生率为9%~50%之间，安慰剂组为1%~13%。
结论：与运动、饮食、生活习惯相结合，与安慰剂相比较，奥利司他对青少年肥胖患者体重的改善更加显著。在这些使用奥利司他1年的青少年人群中尽管出现了胃肠道不良反应，但未见其它不安全事件。
【文献原文】
Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial.
Author:
Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J.
Author Affiliations:
Chanoine JP, MD, PhD: Endocrinology and Diabetes Unit, British Columbia Children’s Hospital, Vancouver;
Hampl S, MD, FAAP: Children’s Mercy Hospitals and Clinics, Kansas City, Mo;
Jensen C, MD: Department of Medicine, Baylor College of Medicine, Houston, Tex;
Boldrin M,MS, Hauptman,MD: JHoffmann-La Roche Inc, Nutley, NJ.
Quote From: The Journal of the American Medical Association. 2005; 293:2873-83
【ABSTRACT】
Context：The prevalence of overweight and obesity in children and adolescents is increasing rapidly. In this population, behavioral therapy alone has had limited success in providing meaningful, sustained weight reduction, and pharmacological treatment has not been extensively studied.
Objective：To determine the efficacy and safety of orlistat in weight management of adolescents.
Design, Setting, and Patients： Multicenter, 54-week (August 2000-October 2002), randomized, double-blind study of 539 obese adolescents (aged 12-16 years; body mass index [BMI] ≥2 units above the 95th percentile) at 32 centers in the United States and Canada.
Interventions：A 120-mg dose of orlistat (n = 357) or placebo (n=182) 3 times daily for 1 year, plus a mildly hypocaloric diet (30% fat calories), exercise, and behavioral therapy.
Main Outcome Measures ：Change in BMI; secondary measures included changes in waist and hip circumference, weight loss, lipid measurements, and glucose and insulin responses to oral glucose challenge.
Results：There was a decrease in BMI in both treatment groups up to week 12, thereafter stabilizing with orlistat but increasing beyond baseline with placebo. At the end of the study, BMI had decreased by 0.55 with orlistat but increased by 0.31 with placebo (P = .001). Compared with 15.7% of the placebo group, 26.5% of participants taking orlistat had a 5% or higher decrease in BMI (P = .005); 4.5% and 13.3%, respectively, had a 10% or higher decrease in BMI (P = .002). At study end, weight had increased 0.53 kg with orlistat and 3.14 kg with placebo (P<.001). Dual-energy x-ray absorptiometry showed that this difference was explained by changes in fat mass. Waist circumference decreased in the orlistat group but increased in the placebo group (–1.33 cm vs +0.12 cm; P<.05). Generally mild to moderate gastrointestinal tract adverse events occurred in 9% to 50% of the orlistat group and in 1% to 13% of the placebo group.
Conclusions：In combination with diet, exercise, and behavioral modification, orlistat statistically significantly improved weight management in obese adolescents compared with placebo. The use of orlistat for 1 year in this adolescent population did not raise major safety issues although gastrointestinal adverse events were more common in the orlistat group.