GLP-1-based therapeutics for cardiorenal protection in metabolic diseases.

With an expanding range of pharmacological options and continuously evolving guidelines, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have garnered substantial clinical and societal attention for their role in T2D and weight management.

随着药物选择范围的不断扩大和指南的不断演变，胰高血糖素样肽-1受体激动剂（GLP-1RAs）因其在T2D和体重管理中的作用而获得了大量的临床和社会关注。

GLP-1RAs have consistently demonstrated robust HbA1c- and body weight-reducing efficacy in clinical and real-world studies.

GLP-1RAs在临床和真实世界研究中一致显示出强大的降低糖化血红蛋白和体重的效果。

In addition, mounting data established their cardiorenal benefits beyond glycaemic control in select high-risk populations.

此外，越来越多的数据表明，在特定高风险人群中，GLP-1RAs的心肾益处超出了血糖控制的范围。

In T2D, GLP-1RAs have been shown to improve both hard cardiovascular and, more recently, relevant kidney outcomes.

在2型糖尿病（T2D）中，GLP-1RAs已被证明可以改善硬性心血管结果，以及最近的相关肾脏结果。

Meanwhile, in individuals with obesity but without T2D, semaglutide (at a higher dose than in T2D) reduces body weight by up to 15% and lowers the risk of major adverse cardiovascular events by 20%.

与此同时，在没有2型糖尿病但体重过重的个体中，与T2D相比更高剂量的semaglutide可以减轻高达15%的体重，并降低主要不良心血管事件的风险达20%。

The success of GLP-1-based therapy fuelled the development of new single molecules that combine GLP-1R agonism with activation of other entero-pancreatic hormone receptors [e.g. glucose-dependent insulinotropic polypeptide (GIP), glucagon and amylin] aiming to achieve complementary and potentially synergistic effects.

GLP-1为基础的治疗成功推动了新的单分子药物的发展，这些药物结合了GLP-1R激动作用和其他肠胰激素受体（例如葡萄糖依赖性胰岛素促进多肽（GIP）、胰高血糖素和淀粉样蛋白）的激活，旨在实现互补和潜在的协同效应。

These next-generation GLP-1-based therapeutics for metabolic diseases, either already available or approaching clinical approval, appear to enhance metabolic and weight-reducing efficacy compared with existing GLP-1RAs.

这些新一代GLP-1为基础的代谢疾病治疗药物，无论是已经上市还是即将进入临床批准阶段，似乎都比现有的GLP-1R激动剂更能增强代谢和减重效果。

An example is tirzepatide, a dual GLP-1/GIP receptor agonist, which has been approved for both T2D and obesity management, demonstrating up to 22.5% weight loss in phase 3 trials.

一个例子是tirzepatide，一种双重GLP-1/GIP受体激动剂，已被批准用于2型糖尿病和肥胖管理，在第三阶段试验中显示出高达22.5%的减重效果。

This review explores the landscape of current and emerging GLP-1-based therapies, their efficacy in managing hyperglycaemia and body weight, recent evidence supporting their cardiorenal benefits and clinical implications of these advancements.

这篇综述探讨了当前和新兴GLP-1基础疗法的概况，它们在管理高血糖和体重方面的疗效，支持它们心脏肾脏益处的最新证据，以及这些进展的临床意义。