Pemafibrate, a selective PPARα modulator, has the beneficial effects on serum triglycerides (TGs) and very low density lipoprotein (VLDL), especially in patients with diabetes mellitus or metabolic syndrome. However, its effect on the low density lipoprotein cholesterol (LDL-C) levels is still undefined. LDL-C increased in some cases together with a decrease in TGs, and the profile of lipids, especially LDL-C, during pemafibrate administration was evaluated. Pemafibrate was administered to type 2 diabetes patients with hypertriglyceridemia. Fifty-one type 2 diabetes patients (mean age 62 ± 13 years) with a high rate of hypertension and no renal insufficiency were analyzed. Pemafibrate 0.2 mg (0.1 mg twice daily) was administered, and serum lipids were monitored every 4–8 weeks from 8 weeks before administration to 24 weeks after administration. LDL-C was measured by the direct method. Lipoprotein fractions were measured by electrophoresis (polyacrylamide gel, PAG), and LDL-migration index (LDL-MI) was calculated to estimate small, dense LDL. Pemafibrate reduced serum TGs, midband and VLDL fractions by PAG. Pemafibrate increased LDL-C levels from baseline by 5.3% (− 3.8–19.1, IQR). Patients were divided into 2 groups: LDL-C increase of > 5.3% (group I, n = 25) and < 5.3% (group NI, n = 26) after pemafibrate. Compared to group NI, group I had lower LDL-C (2.53 [1.96–3.26] vs. 3.36 [3.05–3.72] mmol/L, P = 0.0009), higher TGs (3.71 [2.62–6.69] vs. 3.25 [2.64–3.80] mmol/L), lower LDL by PAG (34.2 [14.5, SD] vs. 46.4% [6.5], P = 0.0011), higher VLDL by PAG (28.2 [10.8] vs. 22.0% [5.2], P = 0.0234), and higher LDL-MI (0.421 [0.391–0.450] vs. 0.354 [0.341–0.396], P < 0.0001) at baseline. Pemafibrate decreased LDL-MI in group I, and the differences between the groups disappeared. These results showed contradictory effects of pemafibrate on LDL-C levels, and these effects were dependent on the baseline levels of LDL-C and TGs. Pemafibrate significantly reduced TGs, VLDL, midband, and small, dense LDL, but increased LDL-C in diabetes patients with higher baseline TGs and lower baseline LDL-C. Even if pre-dose LDL-C remains in the normal range, pemafibrate improves LDL composition and may reduce cardiovascular disease risk.

中文翻译：

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Pemafibrate 降低甘油三酯和小而密的 LDL，但根据基线甘油三酯和 LDL-C 增加 LDL-C：一项观察性研究

Pemafibrate 是一种选择性 PPARα 调节剂，对血清甘油三酯 (TG) 和极低密度脂蛋白 (VLDL) 具有有益作用，特别是对糖尿病或代谢综合征患者。然而，其对低密度脂蛋白胆固醇 (LDL-C) 水平的影响仍未确定。在某些情况下，LDL-C 升高，同时 TG 降低，并且评估了 pemafibrate 给药期间的脂质特征，尤其是 LDL-C。Pemafibrate 用于患有高甘油三酯血症的 2 型糖尿病患者。分析了 51 名高血压发病率高且无肾功能不全的 2 型糖尿病患者（平均年龄 62±13 岁）。给予 Pemafibrate 0.2 mg（0.1 mg，每天两次），并从给药前 8 周至给药后 24 周每 4-8 周监测一次血脂。LDL-C采用直接法测定。通过电泳（聚丙烯酰胺凝胶，PAG）测量脂蛋白分数，并计算低密度脂蛋白迁移指数（LDL-MI）以估计小而密的低密度脂蛋白。Pemafibrate 通过 PAG 降低血清 TG、中带和 VLDL 分数。Pemafibrate 使 LDL-C 水平从基线增加了 5.3%（- 3.8-19.1，IQR）。患者分为 2 组：使用 pemafibrate 后，LDL-C 增加 > 5.3%（I 组，n = 25）和 < 5.3%（NI 组，n = 26）。与 NI 组相比，I 组的 LDL-C 较低（2.53 [1.96-3.26] 与 3.36 [3.05-3.72] mmol/L，P = 0.0009），TGs 较高（3.71 [2.62-6.69] 与 3.25 [2.64] –3.80] mmol/L），PAG 降低 LDL（34.2 [14.5，SD] vs. 46.4% [6.5]，P = 0.0011），PAG 更高 VLDL（28.2 [10.8] vs. 22.0% [5.2]，P = 0.0234)，以及更高的 LDL-MI（0.421 [0.391–0.450] 与 0.354 [0.341–0.396]，P < 0。0001) 在基线。Pemafibrate 降低了 I 组的 LDL-MI，组间差异消失。这些结果表明培马贝特对 LDL-C 水平的影响相互矛盾，这些影响取决于 LDL-C 和 TG 的基线水平。Pemafibrate 显着降低了 TG、VLDL、中带和小而密的 LDL，但增加了基线 TG 较高和基线 LDL-C 较低的糖尿病患者的 LDL-C。即使给药前 LDL-C 保持在正常范围内，pemafibrate 也会改善 LDL 组成并可能降低心血管疾病风险。和小而密的 LDL，但在具有较高基线 TG 和较低基线 LDL-C 的糖尿病患者中增加了 LDL-C。即使给药前的 LDL-C 保持在正常范围内，pemafibrate 也会改善 LDL 的组成并可能降低心血管疾病的风险。和小而密的 LDL，但在具有较高基线 TG 和较低基线 LDL-C 的糖尿病患者中增加了 LDL-C。即使给药前的 LDL-C 保持在正常范围内，pemafibrate 也会改善 LDL 的组成并可能降低心血管疾病的风险。