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[替尔泊肽:2型糖尿病的SURPASS和肥胖症的SURMOUNT临床研究概述]

[Tirzepatide : overview of clinical studies SURPASS in type 2 diabetes and SURMOUNT in obesity].

作者信息

Scheen André

机构信息

Service de Diabétologie, Nutrition et Maladies métaboliques, CHU Liège, Belgique.

Unité de Pharmacologie clinique, Centre Interdisciplinaire de Recherche sur le Médicament (CIRM), ULiège, Belgique.

出版信息

Rev Med Liege. 2024 Dec;79(12):812-820.

Abstract

Tirzepatide is a unimolecular dual agonist of both glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, which has been developed as once-weekly injection first for the treatment of type 2 diabetes (T2DM), then for the treatment of obesity. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, semaglutide 1 mg, basal insulin and preprandial boluses of insulin lispro in six studies of the SURPASS programme. In the SURMOUNT programme, tirzepatide showed a marked reduction in body weight, never reached before with a drug, among people with obesity or overweight associated with complications linked to excess weight. Such weight loss was accompanied by an improvement of comorbidities (as sleep apnea syndrome) and cardiovascular risk factors. Two large cardiovascular outcome trials are ongoing in patients with T2DM (SURPASS-CVOT) and in patients with obesity (SURMOUNT-MMO).

摘要

替尔泊肽是一种胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性促胰岛素多肽(GIP)受体的单分子双重激动剂,最初被开发为每周一次注射剂,用于治疗2型糖尿病(T2DM),随后用于治疗肥胖症。由于这两种肠促胰岛素的作用互补,在SURPASS项目的六项研究中,替尔泊肽以剂量依赖性方式(5、10和15毫克)显示出比安慰剂、司美格鲁肽1毫克、基础胰岛素和门冬胰岛素餐时大剂量注射更好的疗效(糖化血红蛋白和体重降低幅度更大)。在SURMOUNT项目中,替尔泊肽在伴有与超重相关并发症的肥胖或超重人群中显示出显著的体重减轻,这是以往药物从未达到过的。这种体重减轻伴随着合并症(如睡眠呼吸暂停综合征)和心血管危险因素的改善。两项大型心血管结局试验正在进行,一项针对T2DM患者(SURPASS-CVOT),另一项针对肥胖患者(SURMOUNT-MMO)。

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