Patel Dhiren K, Strong Jodi
VA Boston Healthcare System, Boston, Massachusetts, 02130, USA.
Ascension Medical Group, 824 Illinois Ave, Stevens Point, Wisconsin, 54481, USA.
Diabetes Ther. 2019 Oct;10(5):1771-1792. doi: 10.1007/s13300-019-00686-z. Epub 2019 Aug 27.
Type 2 diabetes (T2D) is associated with an increased risk of macro- and microvascular complications, including cardiovascular disease (CVD), heart failure (HF), and chronic kidney disease (CKD). Of the currently available glucose-lowering therapies, sodium-glucose cotransporter-2 inhibitors (SGLT-2is) are the only class to target the pathophysiologic increase in renal glucose reabsorption in patients with T2D. In CV outcomes trials of SGLT-2is in patients with T2D and established CVD or varying levels of CV risk, empagliflozin, canagliflozin, and dapagliflozin were associated with significant improvements in the risk of composite CV and renal outcomes compared with placebo that extended beyond their glycemic effects. Real-world observational studies have also reported improvements in CV outcomes with SGLT-2is compared with other glucose-lowering therapy in routine clinical practice. This review describes the pleiotropic effects of SGLT-2is and discusses the potential mechanisms for these effects as well as how they potentially provide benefits beyond glycemic control in patients with T2D. These favorable nonglycemic effects indicate that SGLT-2is may be of particular benefit in patients with diabetic complications, such as CVD, HF, or CKD. Ongoing large randomized trials in specific patient populations, including those with CVD, HF, or CKD (with or without T2D), may help to confirm the benefits of SGLT-2is in these patients and further elucidate the potential mechanisms of their pleiotropic effects. FUNDING: AstraZeneca.
2型糖尿病（T2D）与大血管和微血管并发症风险增加相关，包括心血管疾病（CVD）、心力衰竭（HF）和慢性肾脏病（CKD）。在目前可用的降糖治疗中，钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）是唯一一类针对T2D患者肾脏葡萄糖重吸收病理生理增加的药物。在T2D合并已确诊CVD或不同程度CV风险患者中进行的SGLT-2i心血管结局试验中，与安慰剂相比，恩格列净、卡格列净和达格列净在复合心血管和肾脏结局风险方面有显著改善，且超出了其降糖作用。真实世界观察性研究也报告称，与常规临床实践中的其他降糖治疗相比，SGLT-2i可改善心血管结局。本综述描述了SGLT-2i的多效性作用，并讨论了这些作用的潜在机制，以及它们如何在T2D患者中潜在地提供超出血糖控制的益处。这些有利的非血糖效应表明，SGLT-2i可能对患有糖尿病并发症（如CVD、HF或CKD）的患者特别有益。正在针对特定患者群体（包括患有CVD、HF或CKD（无论是否合并T2D））进行的大型随机试验，可能有助于证实SGLT-2i对这些患者的益处，并进一步阐明其多效性作用的潜在机制。资助：阿斯利康。
