BACKGROUND Mixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM. METHODS The previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non-HDL-C ≥ 100 mg/dL and TGs ≥ 150 and < 500 mg/dL receiving stable maximally tolerated statin (n = 413). This post hoc subgroup analysis of the primary trial investigated the effects of alirocumab [75 mg every 2 weeks (Q2W) with possible increase to 150 mg Q2W at Week 12] versus usual care [ezetimibe, fenofibrate, or no additional lipid-lowering therapy (LLT)] on non-HDL-C and other lipids in individuals with T2DM and baseline TGs ≥ 200 mg/dL and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). RESULTS Alirocumab significantly reduced non-HDL-C [LS mean difference (standard error (SE)), - 35.0% (3.9)], ApoB [LS mean difference (SE), - 34.7% (3.6)], LDL-C [LS mean difference (SE), - 47.3% (5.2)], LDL particle number [LS mean difference (SE), - 40.8% (4.1)], and Lp(a) [LS mean difference (SE), - 29.9% (5.4)] versus usual care from baseline to Week 24 (all P < 0.0001). Results were similar for alirocumab versus usual care. TG reductions were similar between alirocumab and usual care (no significant difference), but greater with fenofibrate versus alirocumab (P = 0.3371). Overall, alirocumab significantly increased HDL-C versus usual care [LS mean difference (SE), 7.9% (3.6); P < 0.05], although differences with alirocumab versus ezetimibe or fenofibrate were non-significant. Most individuals receiving alirocumab achieved ApoB < 80 mg/dL (67.9%) and non-HDL-C < 100 mg/dL (60.9%). Adverse event frequency was similar between alirocumab (67.2%) and usual care (70.7%). Additionally, no clinically relevant effect of alirocumab on change in glycemic parameters or use of antihyperglycemic agents was observed. CONCLUSIONS Alirocumab is an effective therapeutic option for individuals with T2DM, TGs ≥ 200 mg/dL, and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). Atherogenic lipid (ApoB and non-HDL) reductions were greater with alirocumab than ezetimibe, fenofibrate, or no LLT. Consistent with previous studies, alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov, NCT02642159. Registered December 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02642159.

中文翻译：

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Alirocumab对2型糖尿病，高甘油三酯和低高密度脂蛋白胆固醇患者的影响。

背景技术混合性血脂异常[非高密度脂蛋白胆固醇（non-HDL-C）和甘油三酸酯（TGs）升高，HDL-C降低]在2型糖尿病（T2DM）中很常见，并且与心血管风险增加有关。非HDL-C和载脂蛋白B（ApoB）是混合血脂异常的首选治疗靶标。Alirocumab是针对9型前蛋白转化酶枯草杆菌蛋白酶/ kexin的单克隆抗体（PCSK9），可有效降低低密度脂蛋白胆固醇（LDL-C），非HDL-C，ApoB和脂蛋白（a）（Lp [a]）， T2DM患者的耐受性良好。方法先前报道的开放标签的ODYSSEY DM-DYSLIPIDEMIA试验数据证明了alirocumab对非HDL-C≥100 mg / dL和TGs≥150和<500 mg / dL的患者接受稳定的最大耐受他汀类药物的影响（n = 413 ）。这项主要试验的事后亚组分析调查了与常规治疗（依泽替米贝，非诺贝特或无其他降脂治疗）相比，阿罗洛单抗[每2周75 mg，每12周Q2W可能增加至12 mg Q2W]的效果（ LLT）]对T2DM和基线TG≥200 mg / dL且HDL-C <40 mg / dL（男性）或<50 mg / dL（女性）的个体的非HDL-C和其他脂质。结果Alirocumab显着降低了非HDL-C [LS平均差异（标准误差（SE）），-35.0％（3.9）]，ApoB [LS平均差异（SE），-34.7％（3.6）]，LDL-C [ LS平均差异（SE）-47.3％（5.2）]，LDL粒子数[LS平均差异（SE），-40.8％（4.1）]和Lp（a）[LS平均差异（SE），-29.9％ （5.4）]与从基线到第24周的常规护理相比（所有P <0.0001）。Alirocumab与常规护理的结果相似。Alirocumab和常规护理之间的TG降低相似（无显着差异），但非诺贝特和Alirocumab的TG降低更大（P = 0.3371）。总体而言，与常规治疗相比，alirocumab显着增加了HDL-C [LS平均差异（SE），7.9％（3.6）；P <0.05]，尽管阿洛洛单抗与依折麦布或非诺贝特的差异无统计学意义。接受alirocumab的大多数个体达到ApoB <80 mg / dL（67.9％）和非HDL-C <100 mg / dL（60.9％）。Alirocumab（67.2％）和常规护理（70.7％）之间的不良事件发生频率相似。此外，未观察到阿罗洛单抗对血糖参数变化或使用降糖药的临床相关影响。结论Alirocumab是T2DM，TG≥200 mg / dL，HDL-C <40 mg / dL（男性）或<50 mg / dL（女性）的个体的有效治疗选择。与依泽替米贝，非诺贝特或无LLT相比，阿洛鲁单抗的致动脉性脂质（ApoB和非HDL）降低更大。与以前的研究一致，alirocumab通常耐受性良好。试用注册Clinicaltrials.gov，NCT02642159。于2015年12月24日注册，https：//clinicaltrials.gov/ct2/show/NCT02642159。