Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide.
Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide.
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DOI：
10.1038/ijo.2011.158
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发表时间：
2012-06
期刊：
影响因子：
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通讯作者：
NN8022-1807 Investigators
中科院分区：
文献类型：
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作者：
Astrup A;Carraro R;Finer N;Harper A;Kunesova M;Lean ME;Niskanen L;Rasmussen MF;Rissanen A;Rössner S;Savolainen MJ;Van Gaal L;NN8022-1807 Investigators
在证明了利拉鲁肽在这组肥胖成年人中的短期减肥作用后，我们现在评估安全性/耐受性(主要结果)和持续减肥(次要结果)超过2年的长期疗效。一项在19个欧洲临床研究中心进行的随机、双盲、安慰剂对照的20周研究，延长2年(赞助者在20周内不盲目，参与者/研究人员在1年内)。共有564名成年人(每组90-98人；体重指数30-40 kg m−2)登记，398人进入扩展，268人完成了为期2年的试验。参与者在2周的磨合期间接受饮食(每天缺乏500 )和运动咨询，然后被随机分配(通过电话或基于网络的系统)每天一次皮下注射利拉鲁肽(1.2、1.8、2.4或3.0 mg，n=90-95)、安慰剂(n=98)或开放标签奥利司他(120 mg×3，n=95)。1年后，接受利拉鲁肽/安慰剂治疗的患者改用利拉鲁肽2.4 mg，然后改用3.0 mg(分别基于20周和1年的结果)。这项试验从2007年1月到2009年4月进行，在ClinicalTrials.gov注册，编号NCT00480909。从随机化到1年，服用利拉鲁肽3.0 mg的患者比服用安慰剂的患者多减重5.8 kg(95%可信区间3.7-8.0)，比服用奥利司他的患者多减重3.8 kg(1.6-6.0)(P⩽0.0001；意向治疗、最后观察延续)。在第二年，服用利拉鲁肽2.43.0 mg的受试者(合并组，n=184)比服用奥利司他的受试者(n=95；P<；0.001)减重3.0 kg(1.34.7)。服用利拉鲁肽2.4/3.0 mg(n=92)的受试者在筛选后的2年内体重下降了7.8 kg。添加利拉鲁肽3.0 mg，20周龄体脂减少15.4%，瘦肉减少2.0%。最常见的药物相关副作用为轻至中度、一过性恶心和呕吐。服用利拉鲁肽2.43.0 mg后，糖尿病前期和代谢综合征的两年患病率分别降低了52%和59%，同时血压和血脂也有所改善。利拉鲁肽耐受性良好，可持续减肥2年以上，并可改善心血管危险因素。
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 (P⩽0.0001; 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.