Institut du thorax, CHU Nantes, INSERM, CNRS, UNIV Nantes, 44093 Nantes cedex 1, France.
Li KaShing Knowledge Institute and Keenan Research Centre for Biomedical Science, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
Diabetes Metab. 2017 Oct;43(5):453-459. doi: 10.1016/j.diabet.2017.01.004. Epub 2017 Mar 24.
The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk.
ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening≥70mg/dL (1.81mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24weeks of alirocumab 75mg every 2weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C≥70mg/dL at week 8 underwent a blinded dose increase to 150mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety.
This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017.
The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy.
PCSK9 抑制剂阿利西尤单抗可用于治疗高胆固醇血症，与胰岛素联合用于糖尿病（DM）患者时需要进一步研究。本文描述了一项 IIIb 期研究的原理，旨在评估阿利西尤单抗在高心血管（CV）风险伴高胆固醇血症且接受胰岛素治疗的 1 型（T1）或 2 型（T2）糖尿病患者中的疗效和安全性。
ODYSSEY DM-INSULIN（NCT02585778）是一项随机、双盲、安慰剂对照、多中心研究，计划纳入约 400 例 T2 患者和最多 100 例 T1 胰岛素治疗的 DM 患者。患者在筛选时的低密度脂蛋白胆固醇（LDL-C）水平≥70mg/dL（1.81mmol/L），正在接受最大耐受他汀类药物治疗或不耐受他汀类药物治疗，且正在服用（或未服用）其他降脂药物；还患有已确诊的 CV 疾病或至少有一个其他 CV 危险因素。符合条件的患者以 2:1 的比例随机分为阿利西尤单抗 75mg 每 2 周（Q2W）组或安慰剂组，接受 24 周治疗。LDL-C 在第 8 周≥70mg/dL 的阿利西尤单抗治疗患者在第 12 周接受盲法剂量增加至 150mg Q2W。主要终点为治疗 24 周后计算的 LDL-C 自基线的百分比变化，以及阿利西尤单抗的安全性。
这是一项正在进行的临床试验，纳入了 76 例 T1 患者和 441 例 T2 DM 患者；预计将于 2017 年年中获得结果。
ODYSSEY DM-INSULIN 研究将提供阿利西尤单抗在高 CV 风险且最大耐受他汀类药物治疗未能充分控制的高胆固醇血症的 T1 或 T2 DM 胰岛素治疗患者中的疗效和安全性信息。
