APHM (Assistance Publique-Hôpitaux de Marseille), Department of Nutrition, Metabolic Diseases, Endocrinology, La Conception Hospital, Marseille, France.
Inserm, INRAE (Institut National de Recherche pour l'agriculture, l'Alimentation et l'Environnement), C2VN (Centre de recherche en CardioVasculaire et Nutrition), Aix Marseille University, Marseille, France.
Diabetologia. 2024 Jun;67(6):974-984. doi: 10.1007/s00125-024-06100-z. Epub 2024 Feb 20.
Dyslipidaemias are major cardiovascular risk factors, especially in people with diabetes. In this area, next-generation therapies targeting circulating lipoparticle metabolism (LDL, VLDL, chylomicrons, HDL) have recently been approved by the European and US medical agencies, including anti- proprotein convertase subtilisin/kexin 9 (PCSK9) antibodies; an siRNA targeting PCSK9; bempedoic acid, which targets ATP citrate lyase; an antisense oligonucleotide targeting apolipoprotein C-III; an anti-angiopoietin-like 3 antibody; and a purified omega-3 fatty acid, icosapent ethyl. Other therapies are in different phases of development. There are several important considerations concerning the link between these new lipid-lowering therapies and diabetes. First, since concerns were first raised in 2008 about an increased risk of new-onset diabetes mellitus (NODM) with intensive statin treatment, each new lipid-lowering therapy is being evaluated for its associated risk of NODM, particularly in individuals with prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Second, people with diabetes represent a large proportion of those at high or very high cardiovascular risk in whom these lipid-lowering drugs are currently, or will be, prescribed. Thus, the efficacy of these drugs in subgroups with diabetes should also be closely considered, as well as any potential effects on glycaemic control. In this review, we describe the efficacy of next-generation therapies targeting lipoprotein metabolism in subgroups of people with diabetes and their effects on glycaemic control in individuals with diabetes and prediabetes and in normoglycaemic individuals.
血脂异常是主要的心血管危险因素，尤其是在糖尿病患者中。在这一领域，针对循环脂蛋白代谢（LDL、VLDL、乳糜微粒、HDL）的新一代治疗方法最近已被欧洲和美国的医疗监管机构批准，包括抗前蛋白转化酶枯草溶菌素/糜蛋白酶 9（PCSK9）抗体；靶向 PCSK9 的 siRNA；靶向三磷酸腺苷柠檬酸裂解酶的贝美前列素；靶向载脂蛋白 C-III 的反义寡核苷酸；抗血管生成素样 3 抗体；以及纯化的 ω-3 脂肪酸二十碳五烯酸乙酯。其他疗法处于不同的开发阶段。这些新型降脂疗法与糖尿病之间存在一些重要的关联问题需要考虑。首先，自 2008 年首次提出强化他汀类药物治疗会增加新发糖尿病（NODM）风险以来，每种新的降脂疗法都在评估其与 NODM 的相关性，尤其是在存在糖尿病前期（空腹血糖受损和/或糖耐量受损）的个体中。其次，糖尿病患者在心血管风险高或极高的人群中占很大比例，目前或将来这些降脂药物将被用于这些患者。因此，也应密切关注这些药物在糖尿病亚组中的疗效，以及对血糖控制的任何潜在影响。在这篇综述中，我们描述了靶向脂蛋白代谢的新一代治疗方法在糖尿病亚组中的疗效，以及它们在糖尿病和糖尿病前期以及血糖正常个体中的血糖控制方面的影响。
