Department of Endocrinology and Metabolism, Dokkyo Medical University, Japan.
Department of Endocrinology and Metabolism, Dokkyo Medical University, Japan.
Int J Cardiol. 2021 May 15;331:243-248. doi: 10.1016/j.ijcard.2021.01.063. Epub 2021 Feb 5.
Sodium/glucose cotransporter 2 (SGLT2) inhibitors decrease plasma triglyceride levels and slightly increase low-density lipoprotein (LDL-c) and high-density lipoprotein cholesterol (HDL-c). However, the mechanisms underlying such changes in the blood lipid profile remain to be determined. We investigated how empagliflozin affects plasma markers of cholesterol absorption and synthesis, and evaluated the relationship between changes in these markers and blood lipids in patients with type 2 diabetes.
In a randomized, active-controlled, open-label trial, 51 patients were randomly allocated in 2:1 ratio to receive empagliflozin 10 mg/day (n = 32) or standard therapy (n = 19) for 12 weeks. We measured plasma levels of lathosterol as a marker of cholesterol synthesis, and campesterol and sitosterol as markers of cholesterol absorption, at baseline and 12 weeks after treatment. In the empagliflozin group, serum HDL-c, but not LDL-c, significantly increased between baseline and 12 weeks (54.4 ± 16.3 vs. 58.8 ± 19.6 mg/dl; p = 0.0006), whereas in the standard therapy group, HDL-c and LDL-c remained unchanged. In the empagliflozin group, plasma campesterol also increased significantly (4.14 ± 1.88 vs. 4.90 ± 2.26 μg/ml, p = 0.0008), whereas no change in plasma campesterol or sitosterol was found in the control group. Although plasma lathosterol showed no change in the whole empagliflozin group, it decreased significantly in patients who were not taking statins. In statin non-users, plasma lathosterol decreased significantly after treatment with empagliflozin (2.71 ± 0.99 vs. 1.91 ± 0.99 μg/ml, p < 0.05). In the empagliflozin group, changes in plasma campesterol correlated positively with changes in HDL-c.
Empagliflozin increases serum campesterol, a marker of cholesterol absorption, in patients with type 2 diabetes. This increase may be associated with SGLT2 inhibitor-induced increases in HDL cholesterol.
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂可降低血浆甘油三酯水平，并略微增加低密度脂蛋白胆固醇（LDL-c）和高密度脂蛋白胆固醇（HDL-c）。然而，这种血脂谱变化的机制尚待确定。我们研究了恩格列净如何影响胆固醇吸收和合成的血浆标志物，并评估了 2 型糖尿病患者这些标志物变化与血脂之间的关系。
在一项随机、活性对照、开放标签试验中，51 例患者按 2:1 的比例随机分为恩格列净 10mg/天组（n=32）或标准治疗组（n=19），治疗 12 周。我们在基线和治疗 12 周时测量了血浆中的羊毛固醇（胆固醇合成的标志物）、菜油固醇和谷固醇（胆固醇吸收的标志物）水平。在恩格列净组，血清 HDL-c 但 LDL-c 水平在基线和 12 周之间显著升高（54.4±16.3 与 58.8±19.6mg/dl；p=0.0006），而标准治疗组的 HDL-c 和 LDL-c 无变化。在恩格列净组，血浆菜油固醇也显著增加（4.14±1.88 与 4.90±2.26μg/ml，p=0.0008），而对照组的血浆菜油固醇或谷固醇无变化。尽管整个恩格列净组的血浆羊毛固醇无变化，但在未服用他汀类药物的患者中，其水平显著下降。在未服用他汀类药物的患者中，恩格列净治疗后血浆羊毛固醇显著下降（2.71±0.99 与 1.91±0.99μg/ml，p<0.05）。在恩格列净组，血浆菜油固醇的变化与 HDL-c 的变化呈正相关。
恩格列净增加了 2 型糖尿病患者的血清菜油固醇，这是胆固醇吸收的标志物。这种增加可能与 SGLT2 抑制剂诱导的 HDL 胆固醇增加有关。
