Wu Qian, Zhang Jian, Zhang Fuli, Li Dongnan
Graduate School, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China.
Heilongjiang University of Chinese Medicine, School of Basic Medical Sciences, Harbin, Heilongjiang, China.
Front Endocrinol (Lausanne). 2025 Jun 24;16:1601633. doi: 10.3389/fendo.2025.1601633. eCollection 2025.
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder, and its management has evolved from mere glycemic control to multitarget metabolic regulation. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have demonstrated extensive pleiotropic effects in treating T2DM, and its complications through unique mechanisms. SGLT2is promote urinary glucose excretion, leading to a negative energy balance that triggers lipid metabolic reprogramming and fuel switching in the body. This process significantly reduces visceral fat deposition and improves insulin resistance and the inflammatory status. Additionally, SGLT2is provide a metabolic foundation for cardiovascular, hepatic, and renal protection through multiple pathways, including remodeling cardiac structure, enhancing myocardial metabolism, reducing uric acid levels, and alleviating renal hypoxia. With respect to combination therapy, the pairing of SGLT2is with other hypoglycemic agents and cardiovascular protective drugs has synergistic effects; however, potential adverse reactions should also be considered. Future research should investigate the precise application and long-term safety of SGLT2is as well as develop individualized treatment strategies on the basis of patients' metabolic phenotypes, complications, and drug tolerability to maximize clinical benefits for patients. This review systematically explores the significant roles of SGLT2is in metabolic regulation, cardiovascular protection, and combination therapy, with the aim of providing a comprehensive foundation for optimizing individualized treatment strategies in T2DM management.
2型糖尿病（T2DM）是一种复杂的代谢紊乱疾病，其治疗已从单纯的血糖控制发展为多靶点代谢调节。钠-葡萄糖协同转运蛋白2抑制剂（SGLT2is）已通过独特机制在治疗T2DM及其并发症方面展现出广泛的多效性作用。SGLT2is促进尿糖排泄，导致负能量平衡，从而引发体内脂质代谢重编程和燃料转换。这一过程显著减少内脏脂肪沉积，改善胰岛素抵抗和炎症状态。此外，SGLT2is通过多种途径为心血管、肝脏和肾脏保护提供代谢基础，包括重塑心脏结构、增强心肌代谢、降低尿酸水平和减轻肾脏缺氧。关于联合治疗，SGLT2is与其他降糖药物和心血管保护药物联合具有协同作用；然而，也应考虑潜在的不良反应。未来的研究应探讨SGLT2is的精确应用和长期安全性，并根据患者的代谢表型、并发症和药物耐受性制定个体化治疗策略，以最大限度地为患者带来临床益处。本综述系统地探讨了SGLT2is在代谢调节、心血管保护和联合治疗中的重要作用，旨在为优化T2DM管理中的个体化治疗策略提供全面依据。
