索格列净(一种双重钠-葡萄糖协同转运蛋白2和钠-葡萄糖协同转运蛋白1抑制剂)在心力衰竭治疗中潜在作用的综述

A Review of the Potential Role of Sotagliflozin: A Dual SGLT2 and SGLT1 Inhibitor-in the Treatment of Heart Failure.

作者信息

Tran Bao Anh C, White Raechel T, Bullers Krystal, Cornelio Cyrille K

机构信息

Taneja College of Pharmacy, University of South Florida, Tampa, FL, USA.

University of South Florida Health Libraries, Tampa, FL, USA.

出版信息

J Pharm Technol. 2024 Oct;40(5):248-256. doi: 10.1177/87551225241261040. Epub 2024 Jul 27.

Abstract

This review provides an overview of the pharmacology, efficacy, and safety of sotagliflozin, a dual inhibitor of sodium-glucose cotransporters 1 and 2 (SGLT1 and SGLT2), to reduce the risk of cardiovascular death and hospitalization in those with heart failure. A search of Embase via Elsevier, PubMed, Web of Science-All Databases, and The Cochrane Library for clinical trials in CENTRAL, as well as the MedRxiv and BioRxiv pre-print servers, was conducted from inception through December 1, 2023. Search terms included sotagliflozin, lx 4211, lp 802034, sar 439954, and (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol. Published phase 1, phase 2, and phase 3 clinical trials, meta-analyses, and systematic reviews. Studies were included if they were published in English and evaluated sotagliflozin pharmacology, pharmacokinetics, efficacy, or safety. The Sotagliflozin in Patients with Diabetes and Recent Worsening Heart Failure (SOLOIST-WHF) and Sotagliflozin on Cardiovascular and Renal Events in Patients with Type 2 Diabetes and Moderate Renal Impairment Who Are at Cardiovascular Risk (SCORED) phase 3 trials compared sotagliflozin with placebo in patients with type 2 diabetes mellitus. In both the SCORED and SOLOIST-WHF trials, treatment with sotagliflozin resulted in a statistically significant reduction in the primary composite outcome of death from cardiovascular causes, hospitalizations due to heart failure (HF), and urgent visits for HF. Dual SGLT1 and SGLT2 inhibition with sotagliflozin is efficacious in reducing myocardial infarction (MI), stroke, and HF hospitalizations and urgent visits in the SCORED and SOLOIST-WHF trials. However, its impact on reducing cardiovascular mortality remains uncertain due to premature study discontinuation. Owing to these factors and lack of generalizability, further studies are needed to establish its role in renal protection and cardiovascular mortality in broader populations. At this time, more evidence is warranted to definitively establish sotagliflozin in HF.

摘要

本综述概述了钠-葡萄糖协同转运蛋白1和2(SGLT1和SGLT2)双重抑制剂索格列净的药理学、疗效和安全性,以降低心力衰竭患者心血管死亡和住院的风险。通过爱思唯尔的Embase、PubMed、Web of Science-所有数据库以及CENTRAL中的临床试验的Cochrane图书馆,以及MedRxiv和BioRxiv预印本服务器,从开始到2023年12月1日进行了检索。检索词包括索格列净、lx 4211、lp 802034、sar 439954和(2S,3R,4R,5S,6R)-2-(4-氯-3-(4-乙氧基苄基)phenyl)-6-(甲硫基)四氢-2H-吡喃-3,4,5-三醇。已发表的1期、2期和3期临床试验、荟萃分析和系统评价。如果研究以英文发表并评估了索格列净的药理学、药代动力学、疗效或安全性,则纳入研究。糖尿病合并近期心力衰竭恶化患者的索格列净(SOLOIST-WHF)和2型糖尿病合并中度肾功能损害且有心血管风险患者的索格列净对心血管和肾脏事件的影响(SCORED)3期试验在2型糖尿病患者中将索格列净与安慰剂进行了比较。在SCORED和SOLOIST-WHF试验中,索格列净治疗均导致心血管原因死亡、因心力衰竭(HF)住院和HF紧急就诊的主要复合结局在统计学上显著降低。在SCORED和SOLOIST-WHF试验中,索格列净双重抑制SGLT1和SGLT2在降低心肌梗死(MI)、中风以及HF住院和紧急就诊方面有效。然而,由于研究过早终止,其对降低心血管死亡率的影响仍不确定。由于这些因素以及缺乏普遍性,需要进一步研究以确定其在更广泛人群中肾脏保护和心血管死亡率方面的作用。此时,需要更多证据来明确索格列净在心力衰竭中的作用。

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