L'institut du thorax, INSERM, CNRS, University of Nantes, CHU Nantes, Nantes, France.
CIC INSERM 1413, CHU Nantes, Department of Endocrinology, L'institut du thorax, Nantes, France.
Diabetes Obes Metab. 2019 Apr;21 Suppl 1:39-51. doi: 10.1111/dom.13636.
Diabetic dyslipidaemia, characterized by quantitative, qualitative and kinetic changes in all major circulating lipids, contributes to the increased cardiovascular risk in patients with type 2 diabetes mellitus (T2DM). A promising therapeutic avenue is the inhibition of the proprotein convertase subtilisin kexin 9 (PCSK9) with human monoclonal antibodies (mAbs) that potently reduce plasma low-density lipoprotein cholesterol (LDL-C) levels on top of statin treatment. The aim of this review is to evaluate the efficacy of PCSK9 inhibitors to lower the residual cardiovascular risk of T2DM patients and to discuss the safety of PCSK9 inhibition in these patients. PCSK9 inhibitors potently lower plasma LDL-C levels in T2DM patients and reduce risk for the development of cardiovascular disease. Anti-PCSK9 mAbs are generally not more or less effective in T2DM patients compared to a general high-risk population. Nevertheless, due to their higher cardiovascular risk, the absolute risk reduction of major cardiovascular events is more significant in T2DM patients. This suggests that treatment of T2DM patients with anti-PCSK9 mAbs could be attractive from a cost-effectiveness perspective. Treatment with anti-PCSK9 mAbs did not result in significant treatment-emergent adverse effects. While genetic studies suggest a potential link between PCSK9 inhibition and glucose homeostasis, anti-PCSK9 mAbs did not worsen glycaemic control in T2DM patients, but their safety should be verified after a longer-term follow-up.
糖尿病血脂异常表现为所有主要循环脂质的数量、质量和动力学变化,导致 2 型糖尿病(T2DM)患者心血管风险增加。一种有前途的治疗途径是抑制前蛋白转化酶枯草溶菌素 9(PCSK9),人类单克隆抗体(mAbs)可在他汀类药物治疗的基础上强力降低血浆低密度脂蛋白胆固醇(LDL-C)水平。本综述旨在评估 PCSK9 抑制剂降低 T2DM 患者残余心血管风险的疗效,并讨论这些患者中 PCSK9 抑制的安全性。PCSK9 抑制剂可强力降低 T2DM 患者的血浆 LDL-C 水平,并降低心血管疾病的发病风险。与一般高危人群相比,抗 PCSK9 mAbs 在 T2DM 患者中的疗效并无差异。然而,由于他们的心血管风险较高,T2DM 患者的主要心血管事件绝对风险降低更为显著。这表明,从成本效益的角度来看,用抗 PCSK9 mAbs 治疗 T2DM 患者可能具有吸引力。抗 PCSK9 mAbs 治疗并未导致明显的治疗相关不良反应。虽然遗传研究提示 PCSK9 抑制与糖代谢之间存在潜在联系,但抗 PCSK9 mAbs 并未使 T2DM 患者的血糖控制恶化,但在更长时间的随访后,其安全性仍需验证。
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