Department of Medicine.
Department of Orthopaedic Surgery.
Curr Opin Lipidol. 2024 Oct 1;35(5):253-257. doi: 10.1097/MOL.0000000000000942. Epub 2024 Jul 18.
Inhibitors of sodium-glucose cotransporter-2 (SGLT2) lower renal glucose reabsorption and, thus, are used to treat patients with type 2 diabetes mellitus. Clinical trials coincidentally showed that SGLT2 inhibitors also benefitted patients with heart failure. This review explores the impact of SGLT2 inhibitors on other aspects of cardiovascular disease and skeletal health.
In some, but not all, clinical and preclinical studies, SGLT2 inhibitors are found to reduce serum levels of free fatty acids and triglycerides. Their effects on total and low-density lipoprotein cholesterol and cardiac function also vary. However, SGLT2 inhibitors reduce lipid accumulation in the liver, kidney, and heart, and alter expression of lipid metabolism genes. Effects on free fatty acid uptake in abdominal fat depots depend on the location of adipose tissue. In male, but not female, mice, SGLT2 inhibitors reduce the atherosclerotic lesions and aortic calcium deposition. With respect to skeletal health, recent literature has reported conflicting associations with the risks of fracture and amputation.
Studies suggest that SGLT2 inhibitors reduce tissue lipid accumulation, and in a sex-dependent manner, atherosclerosis and vascular calcification. However, their effects on lipid levels and bone health are complex and remain to be established.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可降低肾脏对葡萄糖的重吸收，因此被用于治疗 2 型糖尿病患者。临床试验偶然发现 SGLT2 抑制剂还可使心力衰竭患者获益。本综述探讨了 SGLT2 抑制剂对心血管疾病和骨骼健康其他方面的影响。
在一些（但不是所有）临床和临床前研究中，SGLT2 抑制剂可降低血清游离脂肪酸和甘油三酯水平。它们对总胆固醇和低密度脂蛋白胆固醇及心功能的影响也存在差异。然而，SGLT2 抑制剂可减少肝脏、肾脏和心脏中的脂质堆积，并改变脂质代谢基因的表达。对腹部脂肪组织中游离脂肪酸摄取的影响取决于脂肪组织的位置。在雄性而非雌性小鼠中，SGLT2 抑制剂可减少动脉粥样硬化病变和主动脉钙沉积。关于骨骼健康，最近的文献报告了与骨折和截肢风险的矛盾关联。
研究表明，SGLT2 抑制剂可减少组织脂质堆积，并以性别依赖的方式减少动脉粥样硬化和血管钙化。然而，其对血脂水平和骨骼健康的影响较为复杂，仍有待进一步证实。
