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利拉鲁肽治疗儿童和青少年2型糖尿病患者
Liraglutide in Children and Adolescents with Type 2 Diabetes


William V. Tamborlane ... 糖尿病 • 2019.08.15
相关阅读
• 利拉鲁肽对2型糖尿病有效 • 应用利拉鲁肽与长期2型糖尿病患者的心血管结局 • 利拉鲁肽对2型糖尿病肾脏结局的影响研究

摘要


背景

二甲双胍是监管部门批准用于大多数早期2型糖尿病青少年患者的首选治疗药物。然而,采用二甲双胍单药治疗可观察到血糖控制效果的早期丧失。目前尚未明确二甲双胍(联用或不联用基础胰岛素治疗)加用利拉鲁肽对青少年2型糖尿病患者是否安全有效。

 

方法

我们以1∶1的比例将10~17岁的患者随机分组,分别在26周双盲期间接受利拉鲁肽(剂量高达1.8 mg/d)或安慰剂皮下给药治疗,随后是26周的开放标签扩展期。纳入标准是体质指数大于第85百分位数,并且糖化血红蛋白水平为7.0%~11.0%(如果患者仅接受饮食和运动干预)或者6.5%~11.0%(如果患者在接受二甲双胍治疗[联用或不联用胰岛素])。试验期间所有患者均接受了二甲双胍治疗。主要终点是26周后的糖化血红蛋白水平相对于基线的变化。次要终点包括空腹血糖水平的变化。试验期间评估了安全性。

 

结果

在被随机分组的135例患者中,134例接受了至少1剂利拉鲁肽(66例患者)或安慰剂(68例患者)治疗。两组的人口统计学特征相似(平均年龄,14.6岁)。在26周后对主要疗效终点进行分析时,利拉鲁肽组的平均糖化血红蛋白水平降低了0.64个百分点,而安慰剂组升高了0.42个百分点,估计的治疗差异为-1.06个百分点(P<0.001);到52周时,差异增加到了-1.30个百分点。在上述两个时间点,利拉鲁肽组的空腹血糖水平均有所降低,而安慰剂组的空腹血糖水平均有所增加。两组报告不良事件的患者数量相似(利拉鲁肽组56例[84.8%],安慰剂组55例[80.9%]),但利拉鲁肽组的不良事件总发生率和胃肠道不良事件发生率较高。

 

结论

在儿童和青少年2型糖尿病患者中,二甲双胍(联用或不联用基础胰岛素)加用剂量高达1.8 mg/d的利拉鲁肽可在52周期间有效改善血糖控制。这一疗效是以胃肠道不良事件发生率增加为代价(由诺和诺德公司资助;Ellipse在ClinicalTrials.gov注册号为NCT01541215)。





作者信息

William V. Tamborlane, M.D., Margarita Barrientos-Pérez, M.M.S.C.I., Udi Fainberg, M.D., Helle Frimer-Larsen, M.Sc., Mona Hafez, M.D., Paula M. Hale, M.D., Muhammad Y. Jalaludin, M.D., Margarita Kovarenko, M.D., Ingrid Libman, M.D., Jane L. Lynch, M.D., Paturi Rao, Ph.D., Naim Shehadeh, M.D., Serap Turan, M.D., Daniel Weghuber, M.D., and Timothy Barrett, Ph.D. for the Ellipse Trial Investigators*
From the Department of Pediatrics, Yale University, New Haven, CT (W.V.T.); Pediatric Endocrinology, Angeles Hospital of Puebla, Puebla City, Mexico (M.B.-P.); Novo Nordisk, Søborg, Denmark (U.F., H.F.-L.); the Diabetes and Endocrinology Unit, Department of Paediatrics, Cairo University, Cairo (M.H.); Novo Nordisk, Plainsboro, NJ (P.M.H.); the Department of Paediatrics, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia (M.Y.J.); Novosibirsk Medical University, Novosibirsk, Russia (M.K.); the Division of Pediatric Endocrinology and Diabetes, UPMC Children’s Hospital of Pittsburgh, Pittsburgh (I.L.); University of Texas Health Science Center at San Antonio, San Antonio (J.L.L.); the Diabetes Research Society, Hyderabad, India (P.R.); the Endocrinology, Diabetes and Metabolism Institute, Rambam Health Care Campus, Haifa, Israel (N.S.); the Department of Pediatrics, Subdivision of Endocrinology and Diabetes, Marmara University School of Medicine, Istanbul, Turkey (S.T.); the Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (D.W.); and the Institute of Cancer and Genomic Sciences, University of Birmingham,and Birmingham Women’s and Children’s Hospital, Birmingham, United Kingdom (T.B.). Address reprint requests to Dr. Tamborlane at the Department of Pediatrics, Yale University, 333 Cedar St., New Haven, CT 06520, or at william.tamborlane@yale.edu. *A complete list of the investigators in the Ellipse trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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