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Diabetes Care述评:“明星药”GLP-1受体激动剂对心血管疾病的全面影响

2021-06-26 MedSci原创 MedSci原创

GLP-1 RA的心血管益处可能不完全是由于动脉粥样硬化斑块的结构变化。

胰高血糖素样肽1受体激动剂(GLP-1 RA)是临床实践中用于改善糖尿病患者血管病(CVD)预后的一个组成部分。大规模的随机对照试验表明,利拉鲁肽、杜拉鲁肽、阿比格鲁肽和塞马鲁肽都能降低糖尿病患者的CVD风险,这些患者要么有已形成的动脉粥样硬化性心血管疾病(ASCVD),要么有高风险特征。

相比之下,艾塞那肽和利塞那肽改善了血糖控制,但在临床试验中对CVD事件没有相当大的影响。一项包括五项随机试验的42920名参与者的荟萃分析表明,GLP-1 RA作为一类药物,与糖尿病和已确定的ASCVD患者的心肌梗死、中风或心血管死亡的综合风险显著降低13%有关。

目前,GLP-1 RA被推荐用于糖尿病患者和已确定的ASCVD或ASCVD的高风险患者。在没有ASCVD(或没有高危指标)的患者中,如果单用生活方式调整和二甲双胍不能达到治疗目标,GLP-RA也可作为二线治疗。

尽管GLP-1RA对CVD的影响已被证明与HbA1c的降低直接相关,但该类药物的多效作用,包括降低收缩压和舒张压、体重和血管炎症,此外还有改善内皮功能已被确定。然而,GLP-1 RA对动脉粥样硬化斑块体积和组成的影响还没有被调查过。

正如近期《糖尿病护理》杂志所报道的,Koska等人研究了GLP-1 RA艾塞那肽是否能改变T2DM患者的颈动脉斑块体积和组成。他们进行了一项安慰剂对照、双盲、务实的随机试验,其中163名参与者被随机分配接受艾塞那肽2mgn = 109)或安慰剂(n = 54),每周一次皮下注射。

基线时颈动脉粥样硬化负担较重的患者被纳入试验,其中大多数呈现出钙化斑块和富含脂质的坏死核心。在基线、9个月和18个月的随访中,尽管与安慰剂相比,每周一次的艾塞那肽的HbA1c平均降低了0.55%,但研究组之间斑块体积随时间的变化没有明显差异。斑块的组成也没有改变,两个治疗组之间在钙化斑块、富含脂质的坏死核心斑块和纤维帽的尺寸变化方面没有发现显著差异。

艾塞那肽每周一次对心脏代谢特征变化的影响

在本研究中观察到的每周一次的艾塞那肽对颈动脉斑块体积和组成缺乏益处,这与艾塞那肽降低心血管事件研究(EXSCEL)试验中对CVD导致的死亡、非致命性心肌梗死或非致命性中风等主要综合终点的适度影响相一致,后者对14752名患者进行了中位数为3.2年的跟踪。

然而,与安慰剂相比,每周一次的艾塞那肽治疗3个月时心率增加9bpm,比GLP-1 RA的临床试验中报告的心率增加更明显,与CVD发生率的降低更相关。鉴于静息心率对CVD结果的预后价值及其与实验性动脉粥样硬化的联系,一周一次的艾塞那肽的心率升高效应可能部分地解释了目前研究中令人失望的颈动脉成像结果。

由此可见, GLP-1 RA的心血管益处可能不完全是由于动脉粥样硬化斑块的结构变化。

参考文献:

Glucagon-Like Peptide 1 Receptor Agonists, Carotid Atherosclerosis, and Cardiovascular Outcomes. Diabetes Care 2021 Jun; 44(6): 1252-1253.https://doi.org/10.2337/dci20-0076

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    2021-08-07 医海拾贝

    希望GLP-1RA找到治疗疾病并减少副作用的恰当剂量,为健康做出贡献

    0

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    2021-06-28 yibei
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