糖尿病药物对抗心力衰竭:药代动力学和药效学特性综述。

IF 3.9 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2022-06-01 Epub Date: 2022-08-02 DOI:10.1080/17425255.2022.2105693
André J Scheen
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引用次数: 7

摘要

心衰(HF)正在成为一个巨大的公共卫生负担。在安慰剂对照试验中,用于2型糖尿病(T2D)的新型糖尿病药物钠-葡萄糖共转运蛋白2型抑制剂(SGLT2is)可降低HF住院率。涉及领域:达格列净和恩格列净的药代动力学(存在肾功能损害和肝功能障碍,两种常与HF相关的合并症)和HF患者的药效学研究。有心血管风险的T2D患者和射血分数降低(HFrEF)或保存(HFpEF)患者的主要HF结局,伴有或不伴有T2D,来自DAPA-HF、EMPEROR-Reduced和EMPEROR-Preserved原始研究结果和事后分析。专家意见:预计心衰患者的SGLT2i药代动力学没有临床相关的变化,而药效学研究报告心肌/血管参数、生物标志物和功能状态有所改善。所有SGLT2is均显示,合并T2D和心血管高危的HF患者住院率显著降低。此外,不管是否存在T2D,达格列净和恩格列净都能改善HFrEF患者的预后。据报道,在HFpEF患者中使用恩格列净也有类似的结果,在一项正在进行的试验(DELIVER)中使用达格列净也得到了证实。因此,SGLT2is为合并或不合并T2D的患者预防和管理HF提供了新的机会。
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Counteracting heart failure with diabetes drugs: a review into the pharmacokinetic and pharmacodynamic properties.

Introduction: Heart failure (HF) is becoming a huge public health burden. New diabetes drugs for type 2 diabetes (T2D), sodium-glucose cotransporter type 2 inhibitors (SGLT2is), reduce the rate of hospitalization for HF in placebo-controlled trials.

Areas covered: Pharmacokinetics of dapagliflozin and empagliflozin (in presence of renal impairment and hepatic dysfunction, two comorbidities frequently associated with HF) and pharmacodynamic studies in patients with HF. Main HF outcomes in T2D patients with cardiovascular risk and in patients with reduced (HFrEF) or preserved (HFpEF) ejection fraction, with or without T2D, from DAPA-HF, EMPEROR-Reduced and EMPEROR-Preserved original findings and post hoc analyses.

Expert opinion: No clinically relevant changes are expected concerning SGLT2i pharmacokinetics in patients with HF while pharmacodynamic studies reported improvements in myocardium/vascular parameters, biomarkers, and functional status. All SGLT2is showed a remarkable reduction in hospitalization for HF in patients with T2D and high cardiovascular risk. Furthermore, both dapagliflozin and empagliflozin improved the prognosis of patients with HFrEF, independently of the presence of T2D. Similar results were reported with empagliflozin in patients with HFpEF, to be confirmed with dapagliflozin in an ongoing trial (DELIVER). Thus, SGLT2is offer a new opportunity for the prevention and management of HF in patients with or without T2D.

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来源期刊
Expert Opinion on Drug Metabolism & Toxicology
Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学
CiteScore
7.90
自引率
2.30%
发文量
62
审稿时长
4-8 weeks
期刊介绍: Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.
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