Department of Medicine, Faculty of Medicine, Barts and the London School of Medicine and Dentistry, UK.
Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, UK.
Int J Cardiol. 2022 Nov 15;367:81-89. doi: 10.1016/j.ijcard.2022.08.015. Epub 2022 Aug 6.
Sacubitril/valsartan is a first-in-class Angiotensin Receptor-Neprilysin inhibitor (ARNi) to be approved for the treatment of heart failure with reduced ejection fraction (HFrEF). The combination tablet has become a mainstay of treatment in the management of heart failure (HF) due to its composite inhibition of the neurohumoral system. There is growing support to show that sacubitril/valsartan may enhance glycaemic control through the augmentation of neprilysin substrates - in particular, glucagon-like peptide 1 (GLP-1). Given that HF and Diabetes Mellitus (DM) frequently coexist, with 44% of patients hospitalised with heart failure also having diabetes as a co-morbidity, it is plausible that sacubitril/valsartan may represent a novel way to address glucose intolerance in HF. However, the role of neprilysin in the degradation of GLP-1 raises important clinical considerations such as the risk of hypoglycaemia and potential drug-drug interactions in patients with and without concurrent DM. We review the current body of research addressing the effect of neprilysin inhibition on GLP-1 receptor signalling and discuss the implications for treatment of HF and DM.
沙库巴曲缬沙坦是首个获批用于射血分数降低的心力衰竭（HFrEF）治疗的血管紧张素受体-脑啡肽酶抑制剂（ARNi）。由于其对神经体液系统的复合抑制作用，该联合片剂已成为心力衰竭（HF）管理治疗的主要药物。越来越多的证据表明，沙库巴曲缬沙坦可能通过增强脑啡肽酶底物（特别是胰高血糖素样肽 1（GLP-1））来改善血糖控制。鉴于心力衰竭和糖尿病（DM）经常同时存在，在因心力衰竭住院的患者中，有 44%同时患有糖尿病作为合并症，沙库巴曲缬沙坦可能代表了一种治疗心力衰竭患者葡萄糖不耐受的新方法。然而，脑啡肽酶在 GLP-1 受体信号转导中的降解作用提出了一些重要的临床问题，例如在有或没有并发 DM 的患者中低血糖的风险和潜在的药物相互作用。我们回顾了目前关于脑啡肽酶抑制对 GLP-1 受体信号转导影响的研究，并讨论了其对心力衰竭和糖尿病治疗的影响。
