Purpose of Review

The micro/macrovascular complications of diabetes cause considerable morbidity and premature mortality. The SGLT2 inhibitors are the first diabetes medications with significant benefits on microvascular disease (nephropathy) and macrovascular cardiovascular disease. In this review, we evaluate one of the potential mechanisms for these cardiorenal benefits—the production of ketones, their benefits, and risks.

Recent Findings

In recent cardiovascular outcome trials (CVOTs), the SGLT2 inhibitors demonstrated significant cardiorenal benefits and they are now approved to reduce CV events/death, heart failure hospitalization, and progression to end-stage renal disease. Glucosuria induced by the SGLT2 inhibitors leads to increased ketone production. Ketones are an efficient fuel source and can improve myocardial and renal function. Further, the ketone body beta-hydroxybutyrate exhibits anti-inflammatory/anti-oxidative actions, which favorably impact myocardial and renal remodeling/fibrosis. Uncontrolled ketogenesis leads to ketoacidosis, especially during conditions of acute illness and excessive insulin dose reductions.

Summary

The SGLT2 inhibitors have demonstrated significant cardiorenal benefits in large CVOTs. Studies are in progress to elucidate whether SGLT2 inhibitor–induced low-grade hyperketonemia contributes to these benefits.

中文翻译：

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钠葡萄糖共转运蛋白2型（SGLT-2）抑制剂和生酮作用：好的和坏的

审查目的

糖尿病的微/微血管并发症导致相当大的发病率和过早死亡。SGLT2抑制剂是首批对微血管疾病（肾病）和大血管心血管疾病具有重大益处的糖尿病药物。在这篇综述中，我们评估了产生这些心血管有益作用的潜在机制之一，即酮的产生，其益处和风险。

最近的发现

在最近的心血管结局试验（CVOT）中，SGLT2抑制剂显示出显着的心肾益处，现已被批准用于减少CV事件/死亡，心力衰竭住院和发展为终末期肾脏疾病。SGLT2抑制剂诱导的糖尿症导致酮产生增加。酮是一种有效的燃料来源，可以改善心肌和肾脏功能。此外，酮体β-羟基丁酸酯显示出抗炎/抗氧化作用，其有利地影响心肌和肾脏的重塑/纤维化。不受控制的生酮作用会导致酮症酸中毒，尤其是在急性疾病和胰岛素剂量减少过多的情况下。

概要

SGLT2抑制剂在大型CVOT中已显示出明显的心肾益处。目前正在进行研究以阐明SGLT2抑制剂引起的低度高酮血症是否有助于这些益处。