SGLT2 Inhibitors in Patients with Heart Failure: A Model-Based Meta-Analysis.

IF 4.6 2区医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacokinetics Pub Date : 2024-11-22 DOI:10.1007/s40262-024-01443-7

Na Wang, Zhen Wu, Jianwei Ren, Xin Zheng, Xiaohong Han

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Abstract

Aims: This study aimed to quantify the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a therapeutic approach for heart failure.

Methods: A systematic literature review was conducted to collect pharmacokinetics (PK) and pharmacodynamics (PD) data on empagliflozin, dapagliflozin, and canagliflozin. Population pharmacokinetic models were developed separately for each drug, along with PK/PD turnover models for SGLT2 inhibitors, to describe the time course of NT-proBNP and simulate its changes over 52 weeks.

Results: A total of 42 publications were included in this study. The results showed that baseline NT-proBNP levels, estimated glomerular filtration rate levels, and body weight significantly influenced the therapeutic effects of SGLT2 inhibitors. Among the studied drugs, canagliflozin demonstrated a greater reduction in NT-proBNP at comparable baseline levels.

Conclusions: Baseline NT-proBNP concentration, renal function, and body weight were covariates affecting the efficacy of SGLT2 inhibitors in reducing NT-proBNP. Canagliflozin showed the most favorable treatment outcomes at similar baseline levels. This model-based meta-analysis approach may support further drug development for SGLT2 inhibitors.

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心力衰竭患者的 SGLT2 抑制剂：基于模型的 Meta 分析。

目的：本研究旨在量化钠-葡萄糖共转运体2（SGLT2）抑制剂对N端前B型钠尿肽（NT-proBNP）的影响，以此作为治疗心力衰竭的一种方法：方法：通过系统性文献综述收集了有关empagliflozin、dapagliflozin和canagliflozin的药代动力学（PK）和药效学（PD）数据。为每种药物分别建立了群体药代动力学模型，并为 SGLT2 抑制剂建立了 PK/PD 循环模型，以描述 NT-proBNP 的时间进程并模拟其在 52 周内的变化：本研究共纳入了 42 篇文献。结果表明，基线 NT-proBNP 水平、估计肾小球滤过率水平和体重对 SGLT2 抑制剂的治疗效果有显著影响。在所研究的药物中，在基线水平相当的情况下，卡格列净（canagliflozin）对NT-proBNP的降幅更大：结论：基线 NT-proBNP 浓度、肾功能和体重是影响 SGLT2 抑制剂降低 NT-proBNP 疗效的协变量。在基线水平相似的情况下，Canagliflozin显示出最有利的治疗效果。这种基于模型的荟萃分析方法可为 SGLT2 抑制剂的进一步药物开发提供支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Pharmacokinetics 医学-药学

CiteScore

8.80

自引率

4.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.