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tirzepatide和司美格鲁肽每周一次给药治疗2型糖尿病患者的比较
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes


Juan P. Frías ... 糖尿病 • 2021.08.05
相关阅读
• 司美格鲁肽治疗与2型糖尿病患者心血管结局关系的研究 • 口服司美格鲁肽与2型糖尿病患者的心血管结局

摘要


背景

tirzepatide是葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1(GLP-1)受体双重激动剂,目前处于研发阶段,用于治疗2型糖尿病。每周一次给药的tirzepatide与司美格鲁肽(选择性GLP-1受体激动剂)的疗效和安全性比较,结果尚不清楚。

 

方法

在一项为期40周的开放标签3期试验中,我们以1∶1∶1∶1的比例将1,879例患者随机分组,4组分别接受5 mg、10 mg或15 mg剂量的tirzepatide或1 mg剂量的司美格鲁肽治疗。基线时,患者的平均糖化血红蛋白水平为8.28%,平均年龄为56.6岁,平均体重为93.7 kg。主要终点是糖化血红蛋白水平从基线至第40周的变化。

 

结果

在5 mg、10 mg和15 mg tirzepatide组中,糖化血红蛋白水平相对于基线的估计平均变化分别为-2.01个百分点、-2.24个百分点和-2.30个百分点,司美格鲁肽组的变化为-1.86个百分点;5 mg、10 mg、15 mg tirzepatide组与司美格鲁肽组的估计差异分别为-0.15个百分点(95%置信区间[CI],-0.28~-0.03;P=0.02)、-0.39个百分点(95% CI,-0.51~-0.26;P<0.001)和-0.45个百分点(95% CI,-0.57~-0.32;P<0.001)。所有剂量的tirzepatide均不劣于司美格鲁肽,甚至优于司美格鲁肽。tirzepatide组的体重降幅超过司美格鲁肽组(最小二乘平均估计差异,分别为-1.9 kg、-3.6 kg和-5.5 kg;所有比较的P<0.001)。在tirzepatide组和司美格鲁肽组中,最常见的不良事件是胃肠道事件,主要为轻度至中度(恶心发生率分别为17%~22%和18%;腹泻发生率分别为13%~16%和12%;呕吐发生率分别为6%~10%和8%)。在接受tirzepatide治疗的患者中,分别有0.6%(5 mg组)、0.2%(10 mg组)和1.7%(15 mg组)报告了低血糖(血糖水平,<54 mg/dL);在接受司美格鲁肽治疗的患者中,0.4%报告了低血糖。tirzepatide组5%~7%的患者和司美格鲁肽组3%的患者报告了严重不良事件。

 

结论

在2型糖尿病患者中,在从糖化血红蛋白水平基线至第40周的平均变化方面,tirzepatide不劣于并且优于司美格鲁肽(由礼来公司资助,SURPASS-2在ClinicalTrials.gov注册号为NCT03987919)。





作者信息

Juan P. Frías, M.D., Melanie J. Davies, M.D., Julio Rosenstock, M.D., Federico C. Pérez Manghi, M.D., Laura Fernández Landó, M.D., Brandon K. Bergman, Pharm.D., Bing Liu, Ph.D., Xuewei Cui, Ph.D., and Katelyn Brown, Pharm.D. for the SURPASS-2 Investigators*
From the National Research Institute, Los Angeles (J.P.F.); the Diabetes Research Centre, University of Leicester, and the National Institute of Health Research Leicester Biomedical Research Centre — both in Leicester, United Kingdom (M.J.D.); the Dallas Diabetes Research Center at Medical City, Dallas (J.R.); Centro de Investigaciones Metabólicas, Buenos Aires (F.C.P.M.); and Eli Lilly, Indianapolis (L.F.L., B.K.B., B.L., X.C., K.B.). Address reprint requests to Dr. Frías at the National Research Institute, 2010 Wilshire Blvd., Ste. 302, Los Angeles, CA 90057, or at juan.frias@nritrials.com. *The SURPASS-2 Investigators are listed in the Supplementary Appendix, available at NEJM.org.

 

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