Impact on Cardiovascular Disease of Sodium-Glucose Cotransporter-2 Inhibitors for the Treatment of Type 2 Diabetes: Where are We Now and What can We Expect?

Type 2 diabetes (T2D) has a close link with cardiovascular disease (CVD), which remains the major cause of mortality in the diabetic population worldwide. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are novel antidiabetic drugs that act by blocking sodium-glucose cotransporter-2 in the renal proximal tubules to inhibit glucose reabsorption and therefore lower blood sugar. SGLT2i have beneficial effects on blood pressure, body weight, albuminuria, uric acid, proinflammatory mediators, and adipokines. Notably, SGLT2i have shown impressive cardioprotection through effects on cardiac fuel energetics, ventricular loading, sodium-hydrogen exchangers, left ventricular remodeling, and cardiomyocyte fibrosis and apoptosis. On the basis of recent large-scale cardiovascular outcome trials (CVOTs) in patients with T2D and established CVD or at high risk of cardiovascular events, SGLT2i protected against cardiovascular mortality and all-cause mortality. Furthermore, SGLT2i lowered the rate of hospitalization for heart failure and progressive kidney disease irrespective of pre-existing CVD or history of heart failure. Dedicated CVOTs have provided a strong evidence of the role of SGLT2i in preventing or slowing the progression of CVD in patients with T2D. This review synthesizes the most cutting-edge insights into the cardioprotective benefits of SGLT2i in individuals with T2D.

關鍵字

Sodium-glucose cotransport-2 inhibitor ； Type 2 diabetes ； Cardiovascular disease ； Cardioprotection ； Heart failure

並列摘要

第二型糖尿病和心血管疾病有著密切的關聯，迄今心血管疾病仍然是造成全球糖尿病族群之中主要的死亡原因。第2型鈉－葡萄糖共同轉運蛋白抑制劑是新型抗糖尿病藥物，主要的機轉是透過阻斷腎臟近曲小管中的第2型鈉－葡萄糖共同轉運蛋白來抑制葡萄糖的再吸收，進而達到降血糖的目的。第2型鈉－葡萄糖共同轉運蛋白抑制劑對於血壓、體重、蛋白尿、尿酸、促發炎介質和脂肪激素等方面的改善是有裨益的。特別的是，第2型鈉－葡萄糖共同轉運蛋白抑制劑能透過多種機轉運用在心臟燃料能量學、心室負荷、鈉－氫交換器、左心室重塑和心肌細胞纖維化及凋亡方面呈現多重心臟保護作用。根據最近大規模心血管結果試驗，針對第二型糖尿病已知合併有心血管疾病或有心血管事件高風險的患者，結果顯示第2型鈉－葡萄糖共同轉運蛋白抑制劑能減少心血管死亡率和整體死亡率。此外，無論是事先已有心血管疾病或心臟衰竭的病史，第2型鈉－葡萄糖共同轉運蛋白抑制劑也能降低心臟衰竭住院和腎臟病惡化的比率。針對第二型糖尿病患者，這些心血管結果試驗已提供了第2型鈉－葡萄糖共同轉運蛋白抑制劑在預防或延緩心血管疾病的角色上一強而有力的證據。本篇綜論以嶄新的視野來探討第2型鈉－葡萄糖共同轉運蛋白抑制劑運用在第二型糖尿病患者之心血管保護的益處。

並列關鍵字