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2型糖尿病患者每周一次Tirzepatide的降糖疗效显著优于索马鲁肽
作者:小柯机器人 发布时间:2021/6/30 23:15:57

美国加州国立研究所Juan P. Frías团队比较了2型糖尿病患者每周接受1次tirzepatide与索马鲁肽治疗的疗效。相关论文于2021年6月25日发表于《新英格兰医学杂志》上。

Tirzepatide是一种双葡萄糖依赖性促胰岛素多肽和胰高血糖素样肽-1(GLP-1)受体激动剂,目前正研发用于治疗2型糖尿病。与选择性GLP-1受体激动剂索马鲁肽相比,每周一次tirzepatide的疗效和安全性尚不清楚。

研究组进行了一项开放标签、40周、3期临床试验,共招募了1879例患者,将其按1:1:1:1的比例随机分组,分别接受剂量为5 mg、10 mg、15 mg的tirzepatide或剂量为1 mg的索马鲁肽进行治疗。这些患者基线时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到40周的变化。

Tirzepatide 5 mg组、10 mg组和15 mg组的糖化血红蛋白水平与基线相比,分别降低2.01、2.24和2.30个百分点,索马鲁肽组则降低1.86个百分点。Tirzepatide 5 mg组、10 mg组和15 mg组与索马鲁肽组之间的估计差异分别为降低0.15、0.39和0.45个百分点。Tirzepatide在所有剂量下均优于索马鲁肽。

Tirzepatide各组的体重减轻幅度显著大于索马鲁肽组。最常见的不良事件是胃肠道不良反应,两组中多为轻中度,其中恶心发生率为18%,腹泻发生率为12%,呕吐发生率为8%。Tirzepatide 5 mg组、10 mg组和15 mg组分别有0.6%、0.2%和1.7%的患者出现低血糖(血糖水平<54 mg/dL),索马鲁肽组中有0.4%。Tirzepatide各组有5-7%的患者发生严重不良事件,索马鲁肽组有3%。

研究结果表明,Tirzepatide治疗2型糖尿病患者,从基线到40周糖化血红蛋白水平的平均变化显著优于索马鲁肽。

附:英文原文

Title: Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes | NEJM

Author: 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.

Issue&Volume: 2021-06-25

Abstract:

Background

Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptor agonist that is under development for the treatment of type 2 diabetes. The efficacy and safety of once-weekly tirzepatide as compared with semaglutide, a selective GLP-1 receptor agonist, are unknown.

Methods

In an open-label, 40-week, phase 3 trial, we randomly assigned 1879 patients, in a 1:1:1:1 ratio, to receive tirzepatide at a dose of 5 mg, 10 mg, or 15 mg or semaglutide at a dose of 1 mg. At baseline, the mean glycated hemoglobin level was 8.28%, the mean age 56.6 years, and the mean weight 93.7 kg. The primary end point was the change in the glycated hemoglobin level from baseline to 40 weeks.

Results

The estimated mean change from baseline in the glycated hemoglobin level was 2.01 percentage points, 2.24 percentage points, and 2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were 0.15 percentage points (95% confidence interval [CI], 0.28 to 0.03; P=0.02), 0.39 percentage points (95% CI, 0.51 to 0.26; P<0.001), and 0.45 percentage points (95% CI, 0.57 to 0.32; P<0.001), respectively. Tirzepatide at all doses was noninferior and superior to semaglutide. Reductions in body weight were greater with tirzepatide than with semaglutide (least-squares mean estimated treatment difference, 1.9 kg, 3.6 kg, and 5.5 kg, respectively; P<0.001 for all comparisons). The most common adverse events were gastrointestinal and were primarily mild to moderate in severity in the tirzepatide and semaglutide groups (nausea, 17 to 22% and 18%; diarrhea, 13 to 16% and 12%; and vomiting, 6 to 10% and 8%, respectively). Of the patients who received tirzepatide, hypoglycemia (blood glucose level, <54 mg per deciliter) was reported in 0.6% (5-mg group), 0.2% (10-mg group), and 1.7% (15-mg group); hypoglycemia was reported in 0.4% of those who received semaglutide. Serious adverse events were reported in 5 to 7% of the patients who received tirzepatide and in 3% of those who received semaglutide.

Conclusions

In patients with type 2 diabetes, tirzepatide was noninferior and superior to semaglutide with respect to the mean change in the glycated hemoglobin level from baseline to 40 weeks.

DOI: 10.1056/NEJMoa2107519

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2107519

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home