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索马鲁肽每周一次给药治疗成人超重或肥胖
Once-Weekly Semaglutide in Adults with Overweight or Obesity


John P.H. Wilding ... 其他 • 2021.03.18
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每周一次,索马鲁肽减肥效果取得历史性突破

 

翁建平

中国科学技术大学生命科学与医学部

 

全球的肥胖症流行带来了巨大的公共卫生挑战。肥胖症不仅增加2型糖尿病的风险,而且还与高血压、血脂异常、心血管疾病和非酒精性脂肪肝等疾病相关,甚至降低预期寿命。尽管饮食和运动为主的生活方式干预是控制体重的基石,但在实践中单纯依靠生活方式干预来减肥和长期维持体重,其效果并不理想。如何有效、安全地减肥和长期维持体重已成为当前医学领域十分棘手、亟待解决的科学与应用难题。

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摘要


背景

肥胖是目前药物治疗方案极少的全球性健康难题。目前尚未证实肥胖成人在生活方式干预措施的基础上接受2.4 mg索马鲁肽(semaglutide)每周一次给药辅助治疗可否减轻体重。

 

方法

在此项双盲试验中,我们纳入了1,961例体质指数(体重[kg]除以[身高{m}的平方])≥30(对于有≥1种体重相关合并症的患者,要求体质指数≥27)且未患糖尿病的成人患者,并以2∶1的比例将其随机分组,两组分别在生活方式干预措施的基础上接受68周索马鲁肽或安慰剂每周一次皮下给药。联合主要终点是体重的变化百分比和体重减轻至少5%。主要被估量(对反映临床试验目的的疗效的精确描述)评估了疗效(不考虑终止治疗或接受挽救干预措施的情况)。

 

结果

从基线至第68周,索马鲁肽组体重的平均变化为-14.9%,而安慰剂组为-2.4%,两组估计差异为-12.4个百分点(95%置信区间[CI],-13.4~-11.5;P<0.001)。第68周时,索马鲁肽组体重减轻≥5%(1,047例参与者[86.4%] vs. 182例[31.5%])、≥10%(838[69.1%] vs. 69[12.0%])和≥15%(612[50.5%] vs. 28[4.9%])的参与者人数超过安慰剂组(所有三项概率比较的P<0.001)。从基线至第68周,索马鲁肽组体重的变化为-15.3 kg,而安慰剂组为-2.6 kg(两组估计差异,-12.7 kg;95% CI,-13.7~-11.7)。与基线相比,索马鲁肽组参与者心脏代谢危险因素的改善幅度,参与者报告的身体功能的提高幅度均超过安慰剂组。恶心和腹泻是索马鲁肽组的最常见不良事件,通常为一过性,严重程度轻度至中度,且随时间推移减轻。索马鲁肽组因胃肠道事件停止治疗的参与者人数超过安慰剂组(59[4.5%] vs. 5[0.8%])。

 

结论

在超重或肥胖参与者中,2.4 mg索马鲁肽每周一次给药联合生活方式干预措施与体重实现有临床意义的持续减轻相关(由诺和诺德公司资助;STEP 1在ClinicalTrials.gov注册号为NCT03548935)。





作者信息

John P.H. Wilding, D.M., Rachel L. Batterham, M.B., B.S., Ph.D., Salvatore Calanna, Ph.D., Melanie Davies, M.D., Luc F. Van Gaal, M.D., Ph.D., Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Barbara M. McGowan, M.D., Ph.D., Julio Rosenstock, M.D., Marie T.D. Tran, M.D., Ph.D., Thomas A. Wadden, Ph.D., Sean Wharton, M.D., Pharm.D., Koutaro Yokote, M.D., Ph.D., Niels Zeuthen, M.Sc., and Robert F. Kushner, M.D. for the STEP 1 Study Group*
From the Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool (J.P.H.W.), University College London Centre for Obesity Research, Division of Medicine, University College London (R.L.B.), the National Institute of Health Research, UCLH Biomedical Research Centre (R.L.B.), the Centre for Weight Management and Metabolic Surgery, University College London Hospital (R.L.B.), and the Department of Diabetes and Endocrinology, Guy’s and St. Thomas’ NHS Foundation Trust (B.M.M.), London, and the Diabetes Research Centre, University of Leicester (M.D.) and the NIHR Leicester Biomedical Research Centre (M.D.), Leicester — all in the United Kingdom; Novo Nordisk, Søborg, Denmark (S.C., M.T.D.T., N.Z.); the Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium (L.F.V.G.); the Departments of Internal Medicine/Endocrinology and Population and Data Sciences, University of Texas Southwestern Medical Center (I.L.), and the Dallas Diabetes Research Center at Medical City (J.R.) — both in Dallas; the Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia (T.A.W.); York University, McMaster University and Wharton Weight Management Clinic, Toronto (S.W.); the Department of Endocrinology, Hematology, and Gerontology, Graduate School of Medicine, Chiba University and Department of Diabetes, Metabolism, and Endocrinology, Chiba University Hospital, Chiba, Japan (K.Y.); and the Division of Endocrinology, Feinberg School of Medicine, Northwestern University, Chicago (R.F.K.). Address reprint requests to Dr. Kushner at Northwestern University Feinberg School of Medicine, 645 N. Michigan Ave., Suite 530, Chicago, IL 60611, or at rkushner@northwestern.edu. *A complete list of investigators in the STEP 1 trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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