Gong Bing, Li Couwen, Shi Zhuang'e, Wang FuPing, Dai Ruanxian, Chen Guobing, Su Heng
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.
Medical School, Kunming University of Science and Technology, Kunming, China.
Front Pharmacol. 2025 Sep 11;16:1675552. doi: 10.3389/fphar.2025.1675552. eCollection 2025.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for type 2 diabetes and obesity, have evolved into multi-organ potential therapeutics due to their pleiotropic effects beyond glycemic control. Mechanistically, GLP-1 signaling modulates immune and inflammatory pathways, regulates autophagy and pyroptosis, alleviates endoplasmic reticulum stress, and interacts with the gut microbiome. These pleiotropic effects provide a rationale for exploring their role in multiple organ systems. Clinical trials have demonstrated cardiovascular and renal protection, leading to additional approvals in high-risk populations. Early data also suggest potential benefits in liver disease, obstructive sleep apnea, chronic respiratory disorders, neurodegenerative and psychiatric conditions, reproductive dysfunction, obesity-associated cancers, and sepsis, although these remain investigational. Therefore, this review aims to synthesize the evidence on the mechanistic expansion of GLP-1RAs from metabolic regulators to systemic modulators of inflammation, autophagy, and organ protection, and explores their therapeutic repurposing across diseases.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）最初是为2型糖尿病和肥胖症开发的，由于其在血糖控制之外的多效性作用，已发展成为具有多器官治疗潜力的药物。从机制上讲，GLP-1信号传导可调节免疫和炎症途径，调节自噬和细胞焦亡，减轻内质网应激，并与肠道微生物群相互作用。这些多效性作用为探索它们在多个器官系统中的作用提供了理论依据。临床试验已证明其具有心血管和肾脏保护作用，从而在高危人群中获得了更多批准。早期数据还表明，其在肝病、阻塞性睡眠呼吸暂停、慢性呼吸系统疾病、神经退行性疾病和精神疾病、生殖功能障碍、肥胖相关癌症和脓毒症中可能具有益处，尽管这些仍在研究中。因此，本综述旨在综合有关GLP-1RAs从代谢调节剂扩展为炎症、自噬和器官保护的全身调节剂的机制证据，并探讨它们在各种疾病中的治疗新用途。
