Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, Frederiksberg C, Denmark.
Int J Obes (Lond). 2012 Jun;36(6):843-54. doi: 10.1038/ijo.2011.158. Epub 2011 Aug 16.
Having demonstrated short-term weight loss with liraglutide in this group of obese adults, we now evaluate safety/tolerability (primary outcome) and long-term efficacy for sustaining weight loss (secondary outcome) over 2 years.
A randomized, double-blind, placebo-controlled 20-week study with 2-year extension (sponsor unblinded at 20 weeks, participants/investigators at 1 year) in 19 European clinical research centers.
A total of 564 adults (n=90-98 per group; body mass index 30-40 kg m(-2)) enrolled, 398 entered the extension and 268 completed the 2-year trial. Participants received diet (500 kcal deficit per day) and exercise counseling during 2-week run-in, before being randomly assigned (with a telephone or web-based system) to once-daily subcutaneous liraglutide (1.2, 1.8, 2.4 or 3.0 mg, n=90-95), placebo (n=98) or open-label orlistat (120 mg × 3, n=95). After 1 year, liraglutide/placebo recipients switched to liraglutide 2.4 mg, then 3.0 mg (based on 20-week and 1-year results, respectively). The trial ran from January 2007-April 2009 and is registered with Clinicaltrials.gov, number NCT00480909.
From randomization to year 1, liraglutide 3.0 mg recipients lost 5.8 kg (95% confidence interval 3.7-8.0) more weight than those on placebo and 3.8 kg (1.6-6.0) more than those on orlistat (P0.0001; intention-to-treat, last-observation-carried-forward). At year 2, participants on liraglutide 2.4/3.0 mg for the full 2 years (pooled group, n=184) lost 3.0 kg (1.3-4.7) more weight than those on orlistat (n=95; P<0.001). Completers on liraglutide 2.4/3.0 mg (n=92) maintained a 2-year weight loss of 7.8 kg from screening. With liraglutide 3.0 mg, 20-week body fat decreased by 15.4% and lean tissue by 2.0%. The most frequent drug-related side effects were mild to moderate, transient nausea and vomiting. With liraglutide 2.4/3.0 mg, the 2-year prevalence of prediabetes and metabolic syndrome decreased by 52 and 59%, with improvements in blood pressure and lipids.
Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors.
在这组肥胖成年人中，我们已经证明了利拉鲁肽具有短期的体重减轻效果，现在评估其在 2 年期间维持体重减轻的安全性/耐受性（主要结局）和长期疗效（次要结局）。
一项随机、双盲、安慰剂对照的 20 周研究，有 2 年的扩展期（赞助商在 20 周时揭盲，参与者/研究者在 1 年时揭盲），在 19 个欧洲临床研究中心进行。
共有 564 名成年人（每组 90-98 人；体重指数 30-40kg/m²）入组，398 人进入扩展期，268 人完成了 2 年试验。参与者在 2 周的导入期内接受饮食（每天热量摄入减少 500kcal）和运动咨询，然后通过电话或网络系统随机分配（n=90-95）接受每日一次皮下注射利拉鲁肽（1.2、1.8、2.4 或 3.0mg）、安慰剂（n=98）或开放标签奥利司他（120mg×3，n=95）。1 年后，利拉鲁肽/安慰剂组患者转为利拉鲁肽 2.4mg，然后转为 3.0mg（分别基于 20 周和 1 年的结果）。该试验于 2007 年 1 月至 2009 年 4 月进行，在 Clinicaltrials.gov 注册，编号为 NCT00480909。
从随机分组到第 1 年，接受利拉鲁肽 3.0mg 的患者比安慰剂组多减轻 5.8kg（95%置信区间 3.7-8.0），比奥利司他组多减轻 3.8kg（1.6-6.0）（P<0.0001；意向治疗，最后观察结转）。第 2 年，接受利拉鲁肽 2.4/3.0mg 完整 2 年的患者（n=184，汇总组）比接受奥利司他的患者多减轻 3.0kg（1.3-4.7）（n=95；P<0.001）。接受利拉鲁肽 2.4/3.0mg 的完成者（n=92）保持了从筛选开始 2 年的体重减轻 7.8kg。接受利拉鲁肽 3.0mg 后，20 周时体脂肪减少了 15.4%，瘦组织减少了 2.0%。最常见的与药物相关的副作用为轻度至中度、短暂的恶心和呕吐。接受利拉鲁肽 2.4/3.0mg 治疗后，2 年内糖尿病前期和代谢综合征的患病率分别降低了 52%和 59%，血压和血脂也得到了改善。
利拉鲁肽耐受性良好，能在 2 年内维持体重减轻，并改善心血管风险因素。
