Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; Laboratório de Investigações NeuroCardíacas, Ciências Médicas de Minas Gerais (LINC CMMG), Belo Horizonte, Minas Gerais, Brazil.
Post-Graduate Program in Health Sciences, Faculdade Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Chem Biol Interact. 2024 Nov 1;403:111229. doi: 10.1016/j.cbi.2024.111229. Epub 2024 Sep 6.
Clinical and preclinical studies have elucidated the favorable effects of Inhibitors of Sodium-Glucose Cotransporter-2 (iSGLT2) in patients and animal models with type 2 diabetes. Notably, these inhibitors have shown significant benefits in reducing hospitalizations and mortality among patients with heart failure. However, despite their incorporation into clinical practice for indications beyond diabetes, the decision-making process regarding their use often lacks a systematic approach. The selection of iSGLT2 remains arbitrary, with only a limited number of studies simultaneously exploring the different classes of them. Currently, no unique guideline establishes their application in both clinical and basic research. This review delves into the prevalent use of iSGLT2 in animal models previously subjected to induced cardiac stress. We have compiled key findings related to cardioprotection across various animal models, encompassing diverse dosages and routes of administration. Beyond their established role in diabetes management, iSGLT2 has demonstrated utility as agents for safeguarding heart health and cardioprotection can be class-dependent among the iSGLT2. These findings may serve as valuable references for other researchers. Preclinical studies play a pivotal role in ensuring the safety of novel compounds or treatments for potential human use. By assessing side effects, toxicity, and optimal dosages, these studies offer a robust foundation for informed decisions, identifying interventions with the highest likelihood of success and minimal risk to patients. The insights gleaned from preclinical studies, which play a crucial role in highlighting areas of knowledge deficiency, can guide the exploration of novel mechanisms and strategies involving iSGLT2.
临床前和临床研究已经阐明了钠-葡萄糖共转运蛋白 2(iSGLT2)抑制剂在 2 型糖尿病患者和动物模型中的有益作用。值得注意的是,这些抑制剂在降低心力衰竭患者的住院率和死亡率方面显示出了显著的益处。然而,尽管它们已被纳入超越糖尿病的适应证的临床实践中,但关于其使用的决策过程往往缺乏系统的方法。iSGLT2 的选择仍然是任意的,只有少数研究同时探索了它们的不同类别。目前,没有独特的指南来确定它们在临床和基础研究中的应用。这篇综述深入探讨了 iSGLT2 在先前经历诱导性心脏应激的动物模型中的普遍应用。我们已经编译了与各种动物模型中不同的 iSGLT2 类别相关的关键心脏保护发现,涵盖了不同的剂量和给药途径。除了它们在糖尿病管理中的既定作用外,iSGLT2 已被证明可用于保护心脏健康,iSGLT2 类药物的心脏保护作用具有依赖性。这些发现可能为其他研究人员提供有价值的参考。临床前研究在确保新化合物或潜在人类用途的治疗方法的安全性方面发挥着关键作用。通过评估副作用、毒性和最佳剂量,这些研究为做出明智决策提供了坚实的基础,确定了最有可能成功且对患者风险最小的干预措施。临床前研究在突出知识缺陷领域方面发挥着至关重要的作用,可以指导对涉及 iSGLT2 的新机制和策略的探索。