PDF(Pubmed)
Abstract：
Obesity is becoming more frequent and has several negative health impacts. Recent advances in weight management strategies have primarily resided in pharmaceutical treatments, and the glucagon-like peptide-1 (GLP-1) receptor agonists have shown great potential in terms of body weight reduction in addition to improving glycemic control in patients with type 2 diabetes (T2D). Recently, the dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist tirzepatide has been developed. Tirzepatide has shown strong effects on glycated hemoglobin (HbA1C) levels in several clinical trials including participants with T2D (SURPASS program). In addition to its lowering effect on HbA1C, tirzepatide leads to substantial reductions in body weight, and a series of clinical trials (SURMOUNT program) have investigated the effects on body weight as the primary outcome. In these two trial programs, tirzepatide in doses of 5 mg to 15 mg administered subcutaneously once weekly resulted in body weight reduction of up to 15% in participants with T2D and up to 21% in participants without T2D, despite comparable baseline bodyweight. Across the two trial programs, adverse effects were mainly gastrointestinal (nausea, diarrhea, and vomiting) occurring with similar incidences of vomiting and lower incidences of diarrhea and nausea in trial participants with T2D compared to trials participants without T2D. Overall, discontinuation due to adverse events occurred in 3-7% of participants with no major differences between individuals with and without T2D. The higher weight-reducing efficacy of tirzepatide in trial participants without T2D is currently unexplained and may be partly reflected in dissimilarities in frequencies of gastrointestinal adverse events. The weight reducing effects of tirzepatide hold great promise for weight management in obese patients regardless of the presence of T2D.
摘要：
肥胖变得越来越频繁,并且具有若干负面的健康影响。体重管理策略的最新进展主要存在于药物治疗中。胰高血糖素样肽-1（GLP-1）受体激动剂除了改善2型糖尿病（T2D）患者的血糖控制外，还在减轻体重方面显示出巨大的潜力。最近,已经开发了GLP-1和葡萄糖依赖性促胰岛素多肽(GIP)受体双重激动剂替西平肽.Tirzepatide在包括T2D（SURPASS计划）参与者在内的多项临床试验中显示出对糖化血红蛋白（HbA1C）水平的强烈影响。除了对HbA1C的降低作用外，tirzepatide导致体重大幅下降，和一系列临床试验（SURMOUNT计划）已经调查了对体重的影响作为主要结果。在这两个试验项目中，每周一次皮下给予5mg至15mg剂量的替西平肽导致T2D参与者的体重减轻高达15％，无T2D参与者的体重减轻高达21％，尽管基线体重相当。在两个试验项目中，不良反应主要是胃肠道(恶心，腹泻,和呕吐）与无T2D的试验参与者相比，有T2D的试验参与者的呕吐发生率相似，腹泻和恶心发生率较低。总的来说,有3-7%的参与者因不良事件停药,有和无T2D的个体之间无主要差异.在没有T2D的试验参与者中，替利西帕肽的较高的减肥功效目前是无法解释的，并且可能部分反映在胃肠道不良事件频率的差异上。无论是否存在T2D，替利西帕肽的减肥作用都为肥胖患者的体重管理带来了巨大的希望。
