Department of Medicine.
Department of Biochemistry.
Curr Opin Lipidol. 2021 Jun 1;32(3):183-190. doi: 10.1097/MOL.0000000000000751.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used antihyperglycemic drugs that show remarkable cardiorenal protective effects in patients with or without type 2 diabetes. Furthermore, they are effective among patients across a wide range of baseline renal and cardiac function. Numerous mechanisms have been evaluated to understand these remarkable clinical benefits. From an early stage, these agents were noted to affect the plasma lipid profile. Here we review lipid profile alterations attributable to SGLT2 inhibitors and also some mechanisms explored in model systems and human studies.
SGLT2 inhibitors given to patients with diabetes as monotherapy shift substrate utilization from carbohydrates to lipids, and have mild effects on the lipid profile. Increased LDL cholesterol appears to be associated with increased hepatic production and decreased catabolism. Increased HDL cholesterol and decreased triglycerides appear to be associated with improved insulin sensitivity and increased lipolysis. Lipid effects of SGLT2 inhibitors are further modulated by background therapy with other diabetes medications and statins.
The minor lipid profile alterations observed in patients treated with SGLT2 inhibitors are offset by the staggering range of beneficial pleiotropic mechanisms that likely explain the marked cardiorenal benefits of these agents.
目的综述:钠-葡萄糖共转运蛋白 2(SGLT2)抑制剂是广泛应用的抗高血糖药物,在有或无 2 型糖尿病的患者中表现出显著的心肾保护作用。此外,它们在广泛的基线肾功能和心功能患者中均有效。为了理解这些显著的临床获益,人们评估了众多机制。从早期开始,这些药物就被注意到可以影响血浆脂质谱。在此,我们综述了归因于 SGLT2 抑制剂的脂质谱改变,并探讨了在模型系统和人体研究中探索到的一些机制。
最新发现:作为单药治疗,给予糖尿病患者 SGLT2 抑制剂会将底物利用从碳水化合物转移到脂质,对脂质谱产生轻微影响。LDL 胆固醇的增加似乎与肝脏产生增加和代谢减少有关。HDL 胆固醇的增加和甘油三酯的减少似乎与胰岛素敏感性的提高和脂肪分解的增加有关。SGLT2 抑制剂的脂质作用还受到其他糖尿病药物和他汀类药物背景治疗的调节。
总结:接受 SGLT2 抑制剂治疗的患者观察到的脂质谱轻微改变被这些药物惊人的多种有益的多效机制所抵消,这些机制可能解释了这些药物在心肾方面的显著益处。