Luo Taimin, Zhang Liaoyun, Tu Kun, Li Gen, Su Hao, Gong Guanli, Huang Yilan, Li Min, Yang Xuping
Department of Pharmacy, Chengdu Seventh People's Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, China.
Department of pharmacy, Sichuan Provincial Woman's and Children's Hospital & The Affliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
Front Immunol. 2025 Jul 3;16:1589341. doi: 10.3389/fimmu.2025.1589341. eCollection 2025.
Autoimmune diseases (AIDs) are conditions where the immune system mistakenly attacks self-antigens, leading to tissue and organ damage. The exact mechanisms underlying AIDs pathogenesis remain unclear, and effective treatments are currently limited, posing significant therapeutic challenges. Recent studies suggest that targeting T cell immune metabolism could be a promising approach for treating AIDs. Repurposed type 2 diabetes mellitus (T2DM) medications, which modulate immune metabolic processes, have shown potential in various inflammatory conditions. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel class of oral antidiabetic agents, not only regulate metabolic dysfunction but also offer protective effects on the heart and kidneys. Emerging preclinical evidence indicates that SGLT2 inhibitors possess immunomodulatory properties, highlighting their potential in enhancing T cell-mediated autoimmune therapy. Clinical studies further validate that SGLT2 inhibitors significantly reduce the risk of chronic kidney disease (CKD) progression in non-diabetic patient groups, such as those with chronic glomerulonephritis like IgA nephropathy. This review aims to evaluate current preclinical and clinical research on the impact of SGLT2 inhibitors on the immune system and explore their mechanisms of action relevant to treating AIDs.
自身免疫性疾病（AIDs）是免疫系统错误地攻击自身抗原，导致组织和器官损伤的病症。AIDs发病机制的具体机制尚不清楚，目前有效的治疗方法有限，带来了重大的治疗挑战。最近的研究表明，靶向T细胞免疫代谢可能是治疗AIDs的一种有前景的方法。用于调节免疫代谢过程的2型糖尿病（T2DM）药物的重新利用，已在各种炎症性疾病中显示出潜力。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是一类新型口服抗糖尿病药物，不仅能调节代谢功能障碍，还对心脏和肾脏具有保护作用。新出现的临床前证据表明，SGLT2抑制剂具有免疫调节特性，突出了它们在增强T细胞介导的自身免疫治疗中的潜力。临床研究进一步证实，SGLT2抑制剂可显著降低非糖尿病患者群体（如患有IgA肾病等慢性肾小球肾炎的患者）慢性肾脏病（CKD）进展的风险。本综述旨在评估目前关于SGLT2抑制剂对免疫系统影响的临床前和临床研究，并探讨其与治疗AIDs相关的作用机制。
