胰高血糖素样受体激动剂和下一代肠促胰岛素药物：代谢、心血管和肾脏益处
Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits.
摘要(中文译文)
GLP-1受体激动剂最初是为治疗2型糖尿病而开发的，对其治疗具有变革性作用，对血糖控制非常有效，具有减轻体重和降低低血糖风险的额外益处。GLP-1受体激动剂可降低主要不良心血管事件（如非致命性心肌梗死、中风和心血管死亡）的风险，以及心力衰竭入院或住院治疗的风险。这些药物可以减少蛋白尿，减缓估计肾小球滤过率随时间的下降，从而延缓或预防肾功能衰竭。此外，GLP-1受体激动剂（如利拉鲁肽和塞马谷肽）以及双葡萄糖依赖性促胰岛素多肽（GIP）和GLP-1受体共激动剂替西帕肽已被批准用于治疗肥胖，临床试验证实了其对各种肥胖相关疾病的益处：预防2型糖尿病；重大心血管不良事件的风险；心力衰竭，尤其是射血分数保持不变；脂肪变性肝病中脂肪变性的消退和纤维化的预防；阻塞性睡眠呼吸暂停和膝骨性关节炎的症状改善。目前的发展包括探索具有提示性疗效证据的新适应症（如神经退行性疾病和物质使用障碍），以及开发用于口服治疗的小分子GLP-1受体激动剂以提高便利性。激活多种受体的双受体（即GLP-1-胰高血糖素和GLP-1-淀粉样蛋白）和三受体（即GIP-GLP-1-胰高糖素）激动剂比单受体激动剂具有更高的疗效，尤其是在减肥方面。然而，一些临床开发项目有很高的胃肠道不良事件负担，应优化剂量递增方案以达到可接受的耐受性。
Abstract
GLP-1 receptor agonists were initially developed to treat type 2 diabetes and have had a transformative effect on its therapy, and are highly effective for glycaemic control, with the added benefit of bodyweight reduction and a low risk of causing hypoglycaemia. GLP-1 receptor agonists reduce risks for major adverse cardiovascular events (eg, non-fatal myocardial infarction, stroke, and cardiovascular death), and the risk of admission to or treatment within hospital for heart failure. These drugs reduce albuminuria and slow the decline in estimated glomerular filtration rate over time, therefore delaying or preventing kidney failure. Furthermore, GLP-1 receptor agonists (eg, liraglutide and semaglutide) and the dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor co-agonist tirzepatide have been approved for treatment of obesity, with clinical trials establishing benefits for various obesity-related conditions: prevention of type 2 diabetes; risk for major adverse cardiovascular events; heart failure, especially with preserved ejection fraction; regression of steatosis and prevention of fibrosis in steatotic liver disease; and symptomatic improvements in obstructive sleep apnoea and knee osteoarthritis. Current developments include the exploration of novel indications (eg, neurodegenerative diseases and substance use disorders) with suggestive evidence of efficacy, and the development of small-molecule GLP-1 receptor agonists for oral treatment to improve convenience. Dual (ie, GLP-1-glucagon and GLP-1-amylin) and triple (ie, GIP-GLP-1-glucagon) receptor agonists activating multiple receptors promise greater efficacy than mono-agonists, especially for weight loss. However, some clinical development programmes have a high burden of adverse gastrointestinal events, and dose-escalation regimens should be optimised to reach acceptable tolerability.
如何引用
AMA
Michael A Nauck, Katherine R Tuttle, Matthias H Tschöp, Matthias Blüher. Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits.. Lancet (London, England). 2026; doi:10.1016/S0140-6736(25)02105-1.
APA
Michael A Nauck, Katherine R Tuttle, Matthias H Tschöp, Matthias Blüher (2026). Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits.. Lancet (London, England). https://doi.org/10.1016/S0140-6736(25)02105-1
GB/T 7714
Michael A Nauck, Katherine R Tuttle, Matthias H Tschöp, Matthias Blüher. Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits.[J]. Lancet (London, England), 2026 doi:10.1016/S0140-6736(25)02105-1.
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