Beyond the Glycaemic Control of Dapagliflozin: Impact on Arterial Stiffness and Macroangiopathy

Abstract

Dapagliflozin is a selective sodium–glucose cotransporter 2 inhibitor (SGLT2i) indicated for the treatment of type 2 diabetes mellitus (T2DM), heart failure with reduced ejection fraction and chronic kidney disease. In all indications, treatment can be initiated in adults with estimated glomerular filtration rate of at least 25 mL/min/1.73 m 2 . As monotherapy or as an additive therapy, dapagliflozin has been shown to promote better glycaemic control, associated with a reduction in body weight and blood pressure in a wide range of patients. In addition, dapagliflozin has a positive impact on arterial stiffness, helps to control the lipid profile and contributes to a reduced risk of cardiovascular complications. This article reviews the current scientific evidence on the role of dapagliflozin in cardiovascular risk factors including arterial stiffness, cardiovascular disease and heart failure in patients with T2DM, with the aim of helping to translate this evidence into clinical practice. The underuse of SGLT2i in actual clinical practice is also discussed.

SGLT2i improves kidney senescence by down‐regulating the expression of LTBP2 in SAMP8 mice

“…Ageing can predispose kidney state into acute and chronic kidney disease. [18][19][20] lowering blood glucose, [22][23][24] the off-target roles of SGLT2i were independent of lowering glucose. 18,19,25 The renal anti-senescence role of SGLT2i has been reported, most likely related to increasing the expression of klotho.…”

“…SGLT2i mainly focus on the sodium‐glucose cotransporter distributed on proximal tubular cells, through promoting the excretion of glucose to lower blood glucose and to exert beneficial effects 21 . Although SGLT2i mainly focus on regulating physiologically glucose level, several researches have demonstrated that SGLT2i played beneficial roles transcending lowering blood glucose, 22–24 the off‐target roles of SGLT2i were independent of lowering glucose 18,19,25 . The renal anti‐senescence role of SGLT2i has been reported, most likely related to increasing the expression of klotho 26,27 .…”

The Importance of SGLT-2 Inhibitors as Both the Prevention and the Treatment of Diabetic Cardiomyopathy

“…The cardioprotective mechanism of SGLT2-is is depicted in Figure 2 . Flozins owe their cardioprotective properties to their effects on haemodynamic parameters such as preload by reducing plasma volume through increased diuresis and decreasing plasma sodium content, and on afterload by lowering arterial pressure and reducing the degree of arterial stiffness [ 32 , 48 , 49 , 50 ]. In addition, flozins have demonstrated a beneficial effect in inhibiting myocardial remodelling and fibrosis and in improving contractile function [ 32 , 51 ].…”

“…Despite the absence of SGLT-2 receptors in the heart, this mechanism of action has been demonstrated for empagliflozin, dapagliflozin and canagliflozin; therefore, it has been identified as a class effect [ 32 ]. SGLT-2 inhibitor drugs also have an impact on CV risk factors by affecting weight loss and lipidogram and by lowering serum uric acid levels [ 50 , 54 ]. Several studies reported lowering of total cholesterol [TC] and triglycerides [TGs], and increases in both high-density lipoproteins [HDLs] and low-density lipoproteins [LDLs] levels during SGLT-2 treatment [ 55 , 56 ].…”