Diuretic effects of sodium–glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and heart failure

Takeuchi, Tetsushiro; Dohi, Kaoru; Omori, Taku; Moriwaki, Keishi; Sato, Yuichi; Nakamori, Shiro; Fujimoto, Naoki; Fujii, Eitaro; Yamada, Norikazu; M, Ito

doi:10.1016/j.ijcard.2015.07.072

Cited by 28 publications

(20 citation statements)

References 9 publications

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“…Takeuchi et al investigated the effect of ipragliflozin on HF status in 20 patients with T2DM. 16 Urine volume was increased from day 1 to day 3 and BNP level was decreased on day 3. The present finding of increased urine volume on day 1 was consistent with the Takeuchi et al study, but in the present study it decreased back down to baseline by day 7.…”

Section: Sglt2i Have Volume-correcting Effectsmentioning

confidence: 91%

Comparison of Canagliflozin, Dapagliflozin and Empagliflozin Added to Heart Failure Treatment in Decompensated Heart Failure Patients With Type 2 Diabetes Mellitus

et al. 2019

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beneficial effect as a class effect on HF condition. 13,14 It remains unclear, however, whether the 3 SGLT2i are similarly effective for HF itself in patients with T2DM. As a preliminary step in the observation of the long-term effectiveness of SGLT2i, it is necessary to confirm the efficacy and safety in the short term. Therefore, the goal of this study was to compare the short-term efficacy and safety of the 3 SGLT2i, canagliflozin, dapagliflozin and empagliflozin in acute decompensated HF patients with T2DM. Methods Subjects This was a single-center, non-randomized, open-label study. This study involved 81 patients who were hospitalized due to decompensated HF complicated with T2DM at Toyama University Hospital. The inclusion criteria were as follows: (1) chronic HF with guideline-directed medical therapy including angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB), β-blockers and diuretics; (2) glycated hemoglobin (HbA1c) before study intervention ≥6.1% in patients with T2DM; (3) age ≥20

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Section: Sglt2i Have Volume-correcting Effectsmentioning

confidence: 91%

Comparison of Canagliflozin, Dapagliflozin and Empagliflozin Added to Heart Failure Treatment in Decompensated Heart Failure Patients With Type 2 Diabetes Mellitus

et al. 2019

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“…For example, in a pilot study involving 20 Japaneses patients with T2D and HF, the addition of ipragliflozin to conventional loop or thiazide diuretics for 4 days decreased plasma natriuretic peptide levels without influencing plasma angiotensin II, aldosterone or noradrenaline levels 84 . It is not known whether participants in EMPA-REG OUTCOME had HFrEF or HFpEF, since echocardiography was not performed at baseline.…”

Section: Mechanisms Of Action Of Sglt2 Inhibitors and Relationships Wmentioning

confidence: 99%

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure

et al. 2017

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Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin – a sodium glucose co-transporter 2 (SGLT2) inhibitor. The CANVAS trial subsequently reported a reduction in 3-point MACE (major adverse cardiovascular events) and HF hospitalization risk. While SGLT2 inhibition may have potential application beyond T2D, including HF, the mechanisms responsible for the cardioprotective effects of SGLT2 inhibitors remain incompletely understood. SGLT2 inhibition promotes natriuresis and osmotic diuresis, leading to plasma volume contraction and reduced preload, as well as decreases in blood pressure, arterial stiffness and afterload, thereby improving subendocardial blood flow in patients with HF. SGLT2 inhibition is also associated with preservation of renal function. Based on data from mechanistic studies and clinical trials, large clinical trials with SGLT2 inhibitors are now investigating the potential use of SGLT2 inhibition in patients with HF with and without T2D. Accordingly, in this review, we summarize key pharmacodynamic effects of SGLT2 inhibitors and the clinical evidence which support the rationale for the use of SGLT2 inhibitors in HF patients with T2D. Since presumably these favorable effects occur independent of blood-glucose lowering, we also explore the potential use of SGLT2 inhibition in patients without T2D with HF or at risk of HF, such as in patients with coronary artery disease or hypertension. Finally, we provide a detailed overview and summary of ongoing cardiovascular outcome trials with SGLT2 inhibitors.

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“…The mode of action of empagliflozin targeting the kidney may mimic that of a diuretic and a "diuretic hypothesis" has been put forward to explain the early and marked CV protection in EMPA-REG OUTCOME [33][34][35][36][37]. Therefore, the comparison of the CV effects of empagliflozin in EMPA-REG OUTCOME with those of different diuretics deserves further attention.…”

Section: ) Meta-analyses Of Trials With Cardiovascular Outcome Resulmentioning

confidence: 99%

“…Because of the reduction in CV mortality occurred already within the first few months, concomitant with a significant reduction in hospitalization for heart failure [30], an haemodynamic rather than an antiatherogenic effect has been suspected [31,32]. This may be attributed to the diuretic (natriuretic/osmotic) activity of the SGLT2 inhibitor, which accompanied the glucuretic effect [33][34][35][36][37], although the so-called "diuretic hypothesis" has also been challenged [38,39].…”

Section: Introductionmentioning

confidence: 99%

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

Scheen

2016

Diabetes Research and Clinical Practice

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Please cite this article as: A.J. Scheen, Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: focus on SGLT2 inhibitors and EMPA-REG OUTCOME, Diabetes Research and Clinical Practice (2016), doi: http://dx.doi.org/10.1016/j.diabres. 2016.09.016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryEmpagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will : 1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; 2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; 3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and 4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis. Although BP reduction associated to empagliflozin therapy may partly contribute to the benefits reported in EMPA-REG OUTCOME, other mechanisms most probably play a greater role in the overall CV protection and reduction in mortality observed in this trial.

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Diuretic effects of sodium–glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and heart failure

Cited by 28 publications

References 9 publications

Comparison of Canagliflozin, Dapagliflozin and Empagliflozin Added to Heart Failure Treatment in Decompensated Heart Failure Patients With Type 2 Diabetes Mellitus

Comparison of Canagliflozin, Dapagliflozin and Empagliflozin Added to Heart Failure Treatment in Decompensated Heart Failure Patients With Type 2 Diabetes Mellitus

Sodium Glucose Cotransporter-2 Inhibition in Heart Failure

Effects of reducing blood pressure on cardiovascular outcomes and mortality in patients with type 2 diabetes: Focus on SGLT2 inhibitors and EMPA-REG OUTCOME

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