Division of Endocrinology and Diabetology, Department of Medicine II, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Department of Clinical Pharmacy, Ain Shams University, 11566 Cairo, Egypt.
Division of Endocrinology and Diabetology, Department of Medicine II, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Mol Metab. 2022 Oct;64:101549. doi: 10.1016/j.molmet.2022.101549. Epub 2022 Jul 18.
Metabolic syndrome and related metabolic disturbances represent a state of low-grade inflammation, which accelerates insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD) progression. Among antidiabetic medications, sodium glucose co-transporter (SGLT) 2 inhibitors are the only agents which showed remarkable reductions in heart failure (HF) hospitalizations and major cardiovascular endpoints (MACE) as well as renal endpoints regardless of diabetes status in large randomized clinical outcome trials (RCTs). Although the exact mechanisms underlying these benefits are yet to be established, growing evidence suggests that modulating inflammation by SGLT2 inhibitors may play a key role.
In this manuscript, we summarize the current knowledge on anti-inflammatory effects of SGLT2 inhibitors as one of the mechanisms potentially mediating their cardiovascular (CV) benefits. We introduce the different metabolic and systemic actions mediated by these agents which could mitigate inflammation, and further present the signalling pathways potentially responsible for their proposed direct anti-inflammatory effects. We also discuss controversies surrounding some of these mechanisms.
SGLT2 inhibitors are promising anti-inflammatory agents by acting either indirectly via improving metabolism and reducing stress conditions or via direct modulation of inflammatory signalling pathways. These effects were achieved, to a great extent, in a glucose-independent manner which established their clinical use in HF patients with and without diabetes.
代谢综合征和相关代谢紊乱表现为低度炎症状态，加速胰岛素抵抗、2 型糖尿病（T2D）和心血管疾病（CVD）的进展。在抗糖尿病药物中，钠-葡萄糖共转运蛋白（SGLT）2 抑制剂是唯一的药物，在大型随机临床结局试验（RCT）中，无论糖尿病状况如何，均显著降低心力衰竭（HF）住院和主要心血管终点（MACE）以及肾脏终点。尽管这些益处的确切机制尚未确定，但越来越多的证据表明，SGLT2 抑制剂通过调节炎症可能发挥关键作用。
在本文中，我们总结了 SGLT2 抑制剂的抗炎作用的现有知识，这是其潜在介导心血管（CV）益处的机制之一。我们介绍了这些药物介导的不同代谢和全身作用，这些作用可以减轻炎症，进一步提出了可能负责其直接抗炎作用的信号通路。我们还讨论了这些机制中的一些争议。
SGLT2 抑制剂是有前途的抗炎药物，通过间接作用（通过改善代谢和减轻应激条件）或通过直接调节炎症信号通路发挥作用。这些作用在很大程度上是葡萄糖非依赖性的，这使其在有或没有糖尿病的 HF 患者中的临床应用得到了确立。
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