司美格鲁肽的3期临床开发（2015-2026）：对试验设计、治疗结局和全球临床经验的综合性循证评价。
完整摘要 · 中文译文
司美格鲁肽是一种长效胰高血糖素样肽-1受体激动剂（GLP-1RA），已成为2型糖尿病（T2DM）、肥胖及相关心脏代谢并发症的重要治疗药物。其延长的药理活性以及皮下和口服制剂的可用性，支持了在不同人群中开展的广泛临床开发。本综述批判性评价了评估司美格鲁肽疗效、安全性和治疗实用性的3期、3a期和3b期临床试验（CT），重点涉及SUSTAIN、PIONEER、STEP、SELECT、FLOW、SOUL及相关研究项目。符合条件的试验根据研究设计、注册、治疗持续时间、人群特征、干预措施、对照药物、主要终点、不良事件（AE）和临床意义进行评估。总体而言，证据表明在特定人群中，血糖控制和体重方面具有临床意义的改善，并具有心血管和肾脏获益。来自肥胖和减重手术后研究的证据进一步支持其在传统血糖管理之外不断扩展的治疗作用。胃肠道事件，尤其是恶心、呕吐、腹泻和便秘，是主要的不良反应，而总体耐受性与已确立的GLP-1RA特征保持一致。然而，人群、治疗持续时间、对照药物和终点定义的差异凸显了重要的证据空白。本综述综合3期临床证据，以界定其不断演变的治疗地位、安全 司美格鲁肽的特征概况及未来研究重点。
完整摘要 · 英文原文
Semaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), has become an important therapeutic agent for type 2 diabetes mellitus (T2DM), obesity, and associated cardiometabolic complications. Its prolonged pharmacological activity and availability as subcutaneous and oral formulations have supported extensive clinical development across diverse populations. This review critically evaluates Phase 3, Phase 3a, and Phase 3b clinical trials (CTs) assessing the efficacy, safety and therapeutic utility of semaglutide, with an emphasis on the SUSTAIN, PIONEER, STEP, SELECT, FLOW, SOUL and related programmes. Eligible trials were assessed according to study design, registration, treatment duration, population characteristics, interventions, comparators, primary endpoints, adverse events (AEs) and clinical significance. Collectively, the evidence demonstrates clinically meaningful improvements in glycaemic control and body weight, as well as cardiovascular and renal benefits, in selected populations. Evidence from obesity and post-bariatric studies further supports its expanding therapeutic role beyond conventional glucose management. Gastrointestinal events, particularly nausea, vomiting, diarrhoea and constipation, were the predominant adverse effects, while overall tolerability remained consistent with the established GLP-1RA profile. However, differences in populations, treatment duration, comparators and endpoint definitions highlight important evidence gaps. This review synthesises Phase 3 clinical evidence to define the evolving therapeutic position, safety profile and future research priorities for semaglutide.