Jensen Thomas Leth, Brønden Andreas, Karstoft Kristian, Sonne David Peick, Christensen Mikkel Bring
Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, DK-2400, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark.
Patient Prefer Adherence. 2024 Feb 8;18:373-382. doi: 10.2147/PPA.S419304. eCollection 2024.
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 (HbA1) levels in several clinical trials including participants with T2D (SURPASS program). In addition to its lowering effect on HbA1, 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.
肥胖正变得越来越常见，并且对健康有多种负面影响。体重管理策略的最新进展主要集中在药物治疗方面，胰高血糖素样肽-1（GLP-1）受体激动剂除了能改善2型糖尿病（T2D）患者的血糖控制外，在减轻体重方面也显示出巨大潜力。最近，双重GLP-1和葡萄糖依赖性促胰岛素多肽（GIP）受体激动剂替尔泊肽已被研发出来。在包括T2D参与者的多项临床试验（SURPASS项目）中，替尔泊肽对糖化血红蛋白（HbA1）水平显示出强效作用。除了降低HbA1的作用外，替尔泊肽还能显著减轻体重，并且一系列临床试验（SURMOUNT项目）已将对体重的影响作为主要结果进行研究。在这两个试验项目中，每周皮下注射一次5毫克至15毫克剂量的替尔泊肽，导致T2D参与者体重减轻高达15%，无T2D参与者体重减轻高达21%，尽管基线体重相当。在这两个试验项目中，不良反应主要是胃肠道反应（恶心、腹泻和呕吐），与无T2D的试验参与者相比，T2D试验参与者呕吐发生率相似，腹泻和恶心发生率较低。总体而言，3%-7%的参与者因不良事件停药，有T2D和无T2D的个体之间没有重大差异。替尔泊肽在无T2D的试验参与者中更高的减重效果目前尚无法解释，可能部分体现在胃肠道不良事件发生频率的差异上。无论是否存在T2D，替尔泊肽的减重作用对肥胖患者的体重管理都有很大前景。
