Clinical Research and Cardiology, Instituto Medico DAMIC / Fundación Rusculleda, Córdoba, Argentina.
CPCLIN - Centro de Pesquisas Clínicas, Rua Goias, São Paulo, Brazil.
Diabetes Obes Metab. 2019 Jun;21(6):1455-1463. doi: 10.1111/dom.13680. Epub 2019 Apr 2.
To evaluate the lipid-lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia.
BERSON was a double-blind, 12-week, phase 3 study (NCT02662569) conducted in 10 countries. Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were randomised 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Co-primary endpoints were the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures, and adverse events (AEs).
Overall, 981 patients were randomised and received ≥1 dose of study drug. Evolocumab significantly reduced LDL-C versus placebo at week 12 (Q2W, -71.8%; QM, -74.9%) and at the mean of weeks 10 and 12 (Q2W, -70.3%; QM, -70.0%; adjusted P < 0.0001 for all) when administered with atorvastatin. Non-high-density lipoprotein cholesterol, apolipoprotein B100, total cholesterol, lipoprotein (a), triglycerides, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol improved significantly with evolocumab versus placebo. The overall incidence of AEs was similar between evolocumab and placebo-treated patients, and there were no clinically meaningful differences in changes over time in glycaemic variables (fasting serum glucose and HbA1c) between the two groups.
In patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.
评估依洛尤单抗联合背景阿托伐他汀在 2 型糖尿病（T2DM）伴高脂血症或混合性血脂异常患者中的降脂疗效和安全性。
BERSON 是一项为期 12 周、双盲、III 期研究（NCT02662569），在 10 个国家进行。年龄≥18 岁且≤80 岁的 T2DM 患者接受阿托伐他汀 20mg/d 治疗，并按 2:2:1:1 的比例随机分为依洛尤单抗 140mg 每 2 周（Q2W）或 420mg 每月（QM）或安慰剂 Q2W 或 QM 组。主要复合终点为自基线至 12 周时及自基线至第 10 和 12 周时平均的低密度脂蛋白胆固醇（LDL-C）的百分比变化。其他终点包括致动脉粥样硬化脂质、血糖指标和不良事件（AE）。
共有 981 例患者接受了至少 1 次研究药物治疗并完成了随机分组。与安慰剂相比，依洛尤单抗在第 12 周（Q2W：-71.8%；QM：-74.9%）和第 10 和 12 周时平均（Q2W：-70.3%；QM：-70.0%；所有均 P＜0.0001）时显著降低 LDL-C，同时非高密度脂蛋白胆固醇、载脂蛋白 B100、总胆固醇、脂蛋白（a）、三酰甘油、高密度脂蛋白胆固醇和极低密度脂蛋白胆固醇也显著改善。依洛尤单抗与安慰剂治疗患者的 AEs 总发生率相似，两组间血糖指标（空腹血糖和 HbA1c）的变化在时间上也无显著差异。
在他汀类药物治疗的 T2DM 伴高脂血症或混合性血脂异常患者中，依洛尤单抗显著降低 LDL-C 和其他致动脉粥样硬化脂质，具有良好的耐受性，对血糖指标无明显影响。
