What Makes Sodium-Glucose Co-Transporter-2 Inhibitors Stand out in Heart Failure?

Khan, Muhammad Shahzeb; Vaduganathan, Muthiah

doi:10.1007/s11892-020-01347-3

Cited by 5 publications

(3 citation statements)

References 43 publications

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“…Angiotensin receptor neprilysin inhibitor (ARNI), beyond blocking angiotensin II signaling, augments natriuretic peptides by inhibiting their breakdown by neprilysin, and becomes class I drug recommended for the treatment of heart failure in the recent years [6]. At present, more attention was paid to the effects of SGLT2i on cardiovascular system [7][8]. A recent nationwide population-based longitudinal cohort study revealed that patients with type 2 diabetes prescribed with SGLT2i were associated with a lower risk of all-cause mortality and new-onset arrhythmias compared with those not taking SGLT2i in real-world practice [9].…”

Section: Introductionmentioning

confidence: 99%

Cardioprotection of Sodium–Glucose Cotransporter 2 Inhibition in Rats With Isoproterenol-Induced Cardiomyopathy

Wang

Wei

et al. 2021

Preprint

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Background: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) has been reported to improve glycaemic control in patients with type 2 diabetes. The aim of this study was to investigate the effect of SGLT2i Dapagliflozin (Dapa) on cardiomyopathy induced by isoproterenol (ISO) and its potential mechanism.Methods: Fifty male Sprague Dawley rats were randomly assigned to Control (n = 10) and ISO (2.5 mg/kg/day)-treated groups (n = 40). After 2 weeks, 28 survived rats with obvious left ventricular dysfunction in ISO group were randomized into three groups for medication including ARNI (angiotensin receptor neprilysin inhibitor, 68 mg/kg/day, n = 9), Dapa (3 mg/kg/day, n = 9) and ISO (saline, n = 10) for 4 weeks. After that, electrical programmed stimulation (EPS) was performed in all groups for the evaluation of the susceptibility of ventricular arrhythmias (VAs). Echocardiography was used to evaluate cardiac function. Results: Echocardiography revealed significant left ventricular (LV) dysfunction in rats with ISO treatment for 2 weeks compared to the control group. Dapa administration for 4 weeks reduced the cumulative risk of death, myocardial fibrosis, plasma angiotensin II level and its functional receptor AT1R protein expression in the heart, and proinflammatory cytokines levels in the cardiac tissue of ISO-treated rats. It also improved cardiac function and inhibited oxidative stress when compared to the ISO group. These effects were similar to ARNI. However, Dapa showed a greater efficacy than ARNI in reducing left ventricular end-diastolic volume, lowing heart rate and VAs, and decreasing body weight and plasma glucose in ISO-treated rats. Conclusion: Dapa effectively improved the myocardial remodelling and oxidative stress like ARNI in ISO-induced cardiomyopathy in rats, but Dapa may be more effectively in decreasing VAs, and improving cardiac function when compared to ARNI. The mechanisms by which Dapa exerts protective effects on cardiomyopathy may be related to its antioxidant capacity and hypoglycemic action.

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Section: Introductionmentioning

confidence: 99%

Cardioprotection of Sodium–Glucose Cotransporter 2 Inhibition in Rats With Isoproterenol-Induced Cardiomyopathy

Wang

Wei

et al. 2021

Preprint

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“…As the global number of patients with type 2 diabetes mellitus (DM2) approaches 500 million, that of patients with heart failure (HF) reaches 64 million. [1][2][3] HF and DM2 often co-occur, resulting in a worse prognosis for both conditions. Records suggest that DM2 can be present in up to 40% of patients with HF and reduced ejection fraction (EF) and up to 45% of those with preserved EF.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 More recently, the beneficial effects of SGLT2 inhibitors on the reduction of cardiovascular events in adequately treated patients with symptomatic HF (New York Heart Association [NYHA] functional class >/= II) with reduced EF (< 40%) led the United States Food and Drug Administration (FDA) and the Brazilian Health Regulatory Agency (Agência Nacional de Vigilância Sanitária; Anvisa) to extend the indication of SGLT2 inhibitors to the treatment of symptomatic HF with reduced EF. 1,4,6 SGLT2 receptors are present in the proximal convoluted tubules of the kidney and mediate glucose uptake, accounting for 90% of renal glucose reabsorption. The inhibition of SGLT2 receptors leads to a reduction in their ability to reabsorb glucose, promoting its excretion in urine and leading to a reduction in plasma glucose levels.…”

Section: Introductionmentioning

confidence: 99%

Possible Mechanisms of Action of SGLT2 Inhibitors in Heart Failure

Martins¹,

Bau²,

Silva³

et al. 2021

ABC: Heart Failure &Amp; Cardiomyopathy

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In mid-2013, sodium-glucose co-transporter 2 (SGLT2) inhibitors such as canagliflozin, dapagliflozin, and empagliflozin were introduced as possible treatments for type 2 diabetes mellitus (DM2). Cardiovascular safety studies demonstrated that not only were SGLT2 inhibitors safe, but they were also associated with a significant reduction in cardiovascular mortality and heart failure (HF) outcomes including hospitalizations. These findings encouraged the development of clinical trials aimed specifically at investigating the effects of this new drug class on HF with reduced ejection fraction (EF), including the DAPA-HF and EMPEROR-reduced studies. The demonstration of beneficial effects of SGLT2 inhibitors on the reduction of cardiovascular events in treated patients with symptomatic HF and reduced left ventricular EF (LVEF < 40 %) resulted in the extension of SGLT2 inhibitor indication to patients with symptomatic HF with reduced EF. The mechanisms behind these beneficial effects of SGLT2 inhibitors are not entirely known. In this review, we analyze several current hypotheses for the cardioprotective effects of SGLT2 inhibitors, including reduced blood pressure, increased natriuresis, improved energy metabolism, prevention of inflammation, weight loss, improved glycemic control, inhibition of the sympathetic nervous system, prevention of myocardial remodeling, prevention of ischemia/ reperfusion injury, inhibition of Na+/H+ channels, increased autophagy and lysosomal degradation, SGLT1 inhibition, reduced hyperuricemia, reduced epicardial fat, increased erythropoietin levels, increased progenitor/precursor cells, reduced oxidative stress, and improved vascular function.

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Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction

Blair

2021

Am J Cardiovasc Drugs

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Dapagliflozin [Farxiga ® (USA); Forxiga ® (EU)], a sodium-glucose cotransporter 2 (SGLT2) inhibitor, was recently approved in the USA and the EU for the treatment of adults with symptomatic heart failure with reduced ejection fraction (HFrEF). The cardiovascular (CV) benefits of dapagliflozin were first observed in the DECLARE-TIMI 58 trial, in which dapagliflozin 10 mg/day significantly reduced the risk of CV death or hospitalization for HF in patients with type 2 diabetes mellitus (T2DM) who had or were at risk for atherosclerotic CV disease. In the subsequent DAPA-HF trial, dapagliflozin 10 mg/day in addition to standard of care was associated with a significantly lower risk of worsening HF or CV death than placebo in patients with HFrEF, regardless of the presence or absence of T2DM. The benefits of dapagliflozin also remained consistent regardless of background HF therapies. Dapagliflozin was generally well tolerated, with an overall safety profile consistent with its known safety profile in other indications. In conclusion, dapagliflozin is an effective and generally well-tolerated treatment that represents a valuable new addition to the options available for symptomatic HFrEF.

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What Makes Sodium-Glucose Co-Transporter-2 Inhibitors Stand out in Heart Failure?

Cited by 5 publications

References 43 publications

Cardioprotection of Sodium–Glucose Cotransporter 2 Inhibition in Rats With Isoproterenol-Induced Cardiomyopathy

Cardioprotection of Sodium–Glucose Cotransporter 2 Inhibition in Rats With Isoproterenol-Induced Cardiomyopathy

Possible Mechanisms of Action of SGLT2 Inhibitors in Heart Failure

Dapagliflozin: A Review in Symptomatic Heart Failure with Reduced Ejection Fraction

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