Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors

Filippatos, Theodosios D.; Tsimihodimos, Vasilis; Elisaf, Moses

doi:10.1080/14656566.2016.1201073

Cited by 41 publications

(23 citation statements)

References 20 publications

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“…Diuresis associated with SGLT2i may cause reduced BP. However, diuresis is a temporary SGLT2i effect, whereas BP reduction from baseline is a sustained effect [ 123 , 128 ].…”

Section: Role Of Sglt and Nhe1 And Nhe3 In Cardiovascular Diseasesmentioning

confidence: 99%

Crosstalk between Sodium–Glucose Cotransporter Inhibitors and Sodium–Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases

Al-Shamasi

Elkaffash

Mohamed

et al. 2021

IJMS

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Abnormality in glucose homeostasis due to hyperglycemia or insulin resistance is the hallmark of type 2 diabetes mellitus (T2DM). These metabolic abnormalities in T2DM lead to cellular dysfunction and the development of diabetic cardiomyopathy leading to heart failure. New antihyperglycemic agents including glucagon-like peptide-1 receptor agonists and the sodium–glucose cotransporter-2 inhibitors (SGLT2i) have been shown to attenuate endothelial dysfunction at the cellular level. In addition, they improved cardiovascular safety by exhibiting cardioprotective effects. The mechanism by which these drugs exert their cardioprotective effects is unknown, although recent studies have shown that cardiovascular homeostasis occurs through the interplay of the sodium–hydrogen exchangers (NHE), specifically NHE1 and NHE3, with SGLT2i. Another theoretical explanation for the cardioprotective effects of SGLT2i is through natriuresis by the kidney. This theory highlights the possible involvement of renal NHE transporters in the management of heart failure. This review outlines the possible mechanisms responsible for causing diabetic cardiomyopathy and discusses the interaction between NHE and SGLT2i in cardiovascular diseases.

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“…Diuresis associated with SGLT2i may cause reduced BP. However, diuresis is a temporary SGLT2i effect, whereas BP reduction from baseline is a sustained effect [ 123 , 128 ].…”

Section: Role Of Sglt and Nhe1 And Nhe3 In Cardiovascular Diseasesmentioning

confidence: 99%

Crosstalk between Sodium–Glucose Cotransporter Inhibitors and Sodium–Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases

Al-Shamasi

Elkaffash

Mohamed

et al. 2021

IJMS

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“…Early theories and evidences have suggested that their antihypertensive effect might derive from a volume-reduction mechanism due to diuresis and natriuresis. In addition, other effects, such as calorie loss, fat-mass decrease, and weight loss, resulting from increasing diuresis and glucosuria also contribute to lowering of blood pressure (34). Furthermore, recent studies have suggested that the ketogenic properties of SGLT2 inhibitors may be a reasonable explanation for their antihypertensive effects independent of renal function (35).…”

Section: Hemodynamic Mechanisms Of Sglt2 Inhibitorsmentioning

confidence: 99%

Mechanisms and Perspectives of Sodium-Glucose Co-transporter 2 Inhibitors in Heart Failure

Zeng

Zhou

Liu

et al. 2021

Front. Cardiovasc. Med.

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Heart failure (HF) is a common complication or late-stage manifestation of various heart diseases. Numerous risk factors and underlying causes may contribute to the occurrence and progression of HF. The pathophysiological mechanisms of HF are very complicated. Despite accumulating advances in treatment for HF during recent decades, it remains an intractable clinical syndrome with poor outcomes, significantly reducing the quality of life and expectancy of patients, and imposing a heavy economic burden on society and families. Although initially classified as antidiabetic agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated reduced the prevalence of hospitalization for HF, cardiovascular death, and all-cause death in several large-scale randomized controlled clinical trials. These beneficial effects of SGLT-2 inhibitors can be attributed to multiple hemodynamic, inflammatory and metabolic mechanisms, not only reducing the serum glucose level. SGLT2 inhibitors have been used increasingly in treatment for patients with HF with reduced ejection fraction due to their surprising performance in improving the prognosis. In addition, their roles and mechanisms in patients with HF with preserved ejection fraction or acute HF have also attracted attention. In this review article, we discuss the possible mechanisms and applications of SGLT2 inhibitors in HF.

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“…Dapagliflozin also met the prespecified criterion for noninferiority to placebo with respect to MACE. Mechanisms that may be involved in the cardioprotective properties of dapagliflozin and generally SGLT2 inhibitors include osmotic diuresis and natriuresis, reductions in plasma volume, blood pressure and arterial stifness and beneficial effects on metabolism 5,53–5556.…”

Section: Effects Of Dapagliflozinmentioning

confidence: 99%

<p>Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes</p>

Papakitsou

Vougiouklakis

Elisaf

et al. 2019

CPAA

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Dapagliflozin belongs in the family of sodium-glucose cotransporter 2 (SGLT2) inhibitors and acts by reducing glucose reabsorption in the proximal tubule. The aim of this review is to present the differential pharmacology and clinical utility of dapagliflozin. Dapagliflozin is orally administered, has a long half-life of 12.9 hours and (similar to empagliflozin) is a much weaker SGLT1 inhibitor compared with canagliflozin. Dapagliflozin significantly decreases glycated hemoglobin and fasting glucose levels in patients with type 2 diabetes mellitus (T2DM). The drug improves body weight, blood pressure, uric acid, triglycerides and high-density lipoprotein cholesterol. In the DECLARE-TIMI 58 trial, a large trial of 17,160 T2DM patients with established cardiovascular disease (CVD) or without established CVD but with multiple risk factors, dapagliflozin compared with placebo resulted in a significantly lower rate of the composite outcome of CVD death or hospitalization for heart failure (HHF); this effect was mainly due to a lower rate of HHF in the dapagliflozin group (HR: 0.73; 95%CI: 0.61–0.88), whereas no difference was observed in the rate of CVD death (HR: 0.98; 95%CI: 0.82–1.17). Moreover, dapagliflozin was noninferior to placebo with respect to major adverse CVD events. Dapagliflozin exerts beneficial effects on albuminuria. Additionally, in the DECLARE-TIMI 58 trial it significantly reduced the composite renal endpoint (40% decrease in glomerular filtration rate, end stage renal disease, or renal death) in both patients with established CVD and patients with multiple risk factors (overall HR: 0.53; 95%CI: 0.43–0.66). However dapagliflozin, like the other SGLT2 inhibitors, is associated with an increased risk of genital and urinary tract infections (usually mild mycotic infections) and acute kidney injury in cases of reduced extracellular volume. Dapagliflozin is a useful antidiabetic treatment which also exerts beneficial effects in the management of heart failure and diabetic kidney disease.

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Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors

Cited by 41 publications

References 20 publications

Crosstalk between Sodium–Glucose Cotransporter Inhibitors and Sodium–Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases

Crosstalk between Sodium–Glucose Cotransporter Inhibitors and Sodium–Hydrogen Exchanger 1 and 3 in Cardiometabolic Diseases

Mechanisms and Perspectives of Sodium-Glucose Co-transporter 2 Inhibitors in Heart Failure

<p>Differential pharmacology and clinical utility of dapagliflozin in type 2 diabetes</p>

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