Hypertension:注意了——DPP4抑制剂和ACEI联用易出现这种副作用!

2022-01-27 MedSci原创 MedSci原创

在同时进行ACEI和DPP4抑制剂时,儿茶酚胺的增加可能导致易患心力衰竭的患者出现心血管并发症。

正常情况下,进餐后小肠分泌肠促胰素,促进餐后胰岛素分泌降低血糖。2型糖尿病患者的肠促胰素效应明显降低,餐后葡萄糖耐量降低。肠促胰素主要包括胰高血糖素样肽-1(GLP-1)和葡萄糖依赖性促胰岛素多肽(GIP),它们极易被DPP-4分解失活。

研究表明,DPP-4抑制剂作为一种新型口服降糖药,具备依赖葡萄糖浓度的降糖机制对β细胞具有改善作用,同时对肾脏具有保护作用。在副作用方面,不会诱发低血糖,不会导致体重增加和肠道副作用。

DPP-4抑制剂代表药物包括西格列汀、利格列汀、维格列汀、沙格列汀、阿格列汀。不同的DPP-4抑制剂在结构和药代动力学上存在明显差异,但均显示出相近的降糖效果和良好的安全性,因此,在降糖治疗中的应用越发广泛。

目前研究表明,DPP4抑制剂可能对心血管产生脱靶效应。其中,DPP4抑制减弱了急性ACEI(血管紧张素转换酶)降压作用,并增加去甲肾上腺素浓度。为此,来自Mayo诊所的专家在一项随机、双盲交叉研究中,比较了与ARB或钙通道阻断剂(CCB)治疗期间相比,DPP4抑制剂在ACEI治疗的影响。结果发表在Hypertension杂志上。

该研究招募了106名患有2型糖尿病和高血压的成年人,100人接受干预。受试者被随机分配到3个血压组之一:雷米普利、缬沙坦或氨氯地平,共15周,并按随机顺序接受3次为期一周的交叉治疗:安慰剂+安慰剂、西格列汀+安慰剂、西格列汀+阿瑞匹坦,中间间隔4周洗脱。

结果显示,DPP4抑制在拉米普利期间增加去甲肾上腺素浓度,但不增加血压。阿瑞匹坦,一种NK1(P物质)受体阻断剂,在使用雷米普利或缬沙坦进行肾素-血管紧张素-醛固酮系统阻断期间降低了立位心率。

DPP4抑制剂对肾素-血管紧张素-醛固酮系统的作用

综上,在同时进行ACEI和DPP4抑制剂时,儿茶酚胺的增加可能导致易患心力衰竭的患者出现心血管并发症。

 

参考文献:

DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor Treatment. HYPERTENSIONAHA.121.18348 https://doi.org/10.1161/HYPERTENSIONAHA.121.18348

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    2022-10-08 hb2008ye
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    2023-01-07 feather89
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    2022-05-25 jklm09
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    2022-01-27 oliver176

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