scholarly journals Sodium glucose cotransporter 2 inhibitors: mechanisms of action in heart failure

2020 ◽  
Author(s):  
Mieczysław Dutka ◽  
Rafał Bobiński ◽  
Izabela Ulman-Włodarz ◽  
Maciej Hajduga ◽  
Jan Bujok ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glycaemic Control ◽  
Experimental Studies ◽  
Mechanisms Of Action ◽  
New Class ◽  
Current State ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Clinical Benefits ◽  
Treatment Of Diabetes

Abstract Diabetes is a key independent risk factor in the development of heart failure (HF) and a strong, adverse prognostic factor in HF patients. HF remains the primary cause of hospitalisation for diabetics and, as previous studies have shown, when HF occurs in these patients, intensive glycaemic control does not directly improve the prognosis. Recent clinical studies assessing a new class of antidiabetic drugs, sodium-glucose cotransporter 2 inhibitors (SGLT2is) showed some unexpected beneficial results. Patients treated with SGLT2is had a significant decrease in both cardiovascular (CV) and all-cause mortality and less hospitalisations due to HF compared to those given a placebo. These significant clinical benefits occurred quickly after the drugs were administered and were not solely due to improved glycaemic control. These groundbreaking clinical trials’ results have already changed clinical practice in the management of patients with diabetes at high CV risk. These trials have triggered numerous experimental studies aimed at explaining the mechanisms of action of this unique group of drugs. This article presents the current state of knowledge about the mechanisms of action of SGLT2is developed for the treatment of diabetes and which, thanks to their cardioprotective effects, may, in the future, become a treatment for patients with HF.

scholarly journals Sodium–glucose Cotransporter 2 Inhibitors in Heart Failure: Potential Mechanisms of Action, Adverse Effects and Future Developments

2019 ◽  
Vol 14 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Juan Tamargo
Keyword(s):  
Heart Failure ◽  
Glycaemic Control ◽  
Adverse Effects ◽  
Major Cardiovascular Events ◽  
Sodium Glucose Cotransporter ◽  
Urinary Glucose ◽  
Patients With Diabetes ◽  
Near Future ◽  
Glucose Excretion

Heart failure is a common complication in patients with diabetes, and people with both conditions present a worse prognosis. Sodium– glucose cotransporter 2 inhibitors (SGLT2Is) increase urinary glucose excretion, improving glycaemic control. In type 2 diabetes (T2D), some SGLT2Is reduce major cardiovascular events, heart failure hospitalisations and worsening of kidney function independent of glycaemic control. Multiple mechanisms (haemodynamic, metabolic, hormonal and direct cardiac/renal effects) have been proposed to explain these cardiorenal benefits. SGLT2Is are generally well tolerated, but can produce rare serious adverse effects, and the benefit/risk ratio differs between SGLT2Is. This article analyses the mechanisms underlying the cardiorenal benefits and adverse effects of SGLT2Is in patients with T2D and heart failure and outlines some questions to be answered in the near future.

scholarly journals Sodium glucose cotransporter (SGLT)-2 inhibitors alleviate the renal stress responsible for sympathetic activation

2020 ◽  
Vol 14 ◽  
pp. 175394472093938
Author(s):  
Motoaki Sano
Keyword(s):  
Heart Failure ◽  
Renal Failure ◽  
Animal Experiments ◽  
Kidney Injury ◽  
Sympathetic Activation ◽  
Abnormal Glucose Metabolism ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Cardiac Condition ◽  
Cortical Ischemia

This review focuses on the pathogenic role of sodium glucose cotransporter (SGLT)-2 in the development of renal dysfunction and heart failure in patients with diabetes, by emphasizing the concept of reno-cardiac syndrome (kidney injury worsens cardiac condition) and by substantiating the deleterious effect of sympathetic overdrive in this context. Furthermore, the review proposes a mechanistic hypothesis to explain the benefits of SGLT2 inhibitors, specifically that SGLT-2 inhibitors reduce sympathetic activation at the renal level. To illustrate this point, several examples from both animal experiments and clinical observations are introduced. The bidirectional interaction of the heart and kidney were deeply implicated as an exacerbator of heart failure and renal failure without diabetes. Renal cortical ischemia and abnormal glucose metabolism of tubular epithelial cells are likely to exist as common pathologies in nondiabetic heart failure patients. It is no wonder why SGLT-2 inhibitors are specifically being studied even in the absence of diabetes, both for heart failure and also for renal failure.

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

Diabetes und Herzinsuffizienz

2019 ◽  
Vol 14 (03) ◽  
pp. 180-192
Author(s):  
Philipp H. Baldia ◽  
Nikolaus Marx ◽  
Katharina A. Schütt
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Early Stage ◽  
Hospitalization Rates ◽  
Patients With Heart Failure ◽  
Patients With Diabetes ◽  
Treatment Of Diabetes ◽  
The Common ◽  
Current Guidelines ◽  
Positive Effect

AbstractDiabetes mellitus is a very important comorbidity in patients with heart failure, as the common presence of both diseases significantly worsens the prognosis of patients. In order to improve the outcome of these patients, it is essential to diagnose both diseases at an early stage and to treat them in accordance with guidelines. In particular, a differentiated medication plays a crucial role. The therapy of heart failure does not differ in patients with diabetes and patients without diabetes. In the treatment of diabetes mellitus, however, it is very important to choose substances that have a positive effect on the cardiovascular outcome of patients. First-line treatment of diabetes in patients with cardiovascular diseases should be metformin, followed by a SGLT-2 inhibitor or GLP-1 receptor agonist with proven cardiac benefit. A rigorous adjustment of risk factors according to current guidelines reduces cardiovascular mortality and hospitalization rates. Glitazones and saxagliptin are associated with increased hospitalization rates and should be avoided in heart failure.

Cardio-protective effects of sodium-glucose co-transporter 2 inhibitors: focus on heart failure

2020 ◽  
Vol 26 ◽  
Author(s):  
Dimos Karangelis ◽  
C. David Mazer ◽  
Dimitrios Stakos ◽  
Aphrodite Tzifa ◽  
Spiros Loggos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Mechanisms Of Action ◽  
Sglt2 Inhibitors ◽  
Protective Effects ◽  
Reduced Ejection Fraction ◽  
Risk Of Death ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Energetics

Background: Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabetes and either established cardiovascular disease (CV) or multiple CV risk factors. Objective: Herein we aim to focus on the role of SGLT2 inhibitors regarding the improvement in heart failure outcomes and the proposed mechanisms of action by which these drugs confer their beneficial effect. Methods: PubMed, Embase and Google Scholar databases were searched to identify eligible articles which are comprehensively summarized and discussed. Results: The most commonly discussed mechanisms of action are diuresis and natriuresis, reduction in preload, afterload, and ventricular mass, as well as stimulation of erythropoietin production and improved myocardial energetics. SGLT2 inhibitors improve outcomes in patients with established heart failure (HF) and reduce the risk of death and HF admissions in patients with established chronic HF with reduced ejection fraction (HFrEF), either with or without diabetes. Conclusion: Potential key mechanisms that may explain the notable cardioprotective benefits of SGLT2 inhibitors have been outlined. These agents have recently received class Ia recommendation in specific groups of people with DM to lower the risk of hospitalization for HF and risk of death, while these benefits may also extend to people without diabetes. It remains to be seen whether they will also emerge as treatment approaches in the acute phase of CV episodes.

scholarly journals Lessons learned from the DAPA-HF trial concerning the mechanisms of benefit of SGLT2 inhibitors on heart failure events in the context of other large-scale trials nearing completion

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Milton Packer
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Lessons Learned ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Artery Disease

Abstract Four large-scale trials in type 2 diabetes have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the occurrence of serious heart failure events. Additionally, the DAPA-HF trial demonstrated a benefit of dapagliflozin to reduce major adverse outcomes in patients with established heart failure with a reduced ejection fraction. The trial sheds light on potential mechanisms. In DAPA-HF, the benefits of dapagliflozin on heart failure were seen to a similar extent in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related cardiotoxicity. The action of SGLT2 inhibitors to promote ketogenesis is also primarily a feature of the action of these drugs in patients with diabetes, raising doubts that enhanced ketogenesis contributes to the benefit on heart failure. Also, dapagliflozin does not have a meaningful effect to decrease circulating natriuretic peptides, and it did not potentiate the actions of diuretics in DAPA-HF; moreover, intensification of diuretics therapy does not reduce cardiovascular death, questioning a benefit of SGLT2 inhibitors that is mediated by an action on renal sodium excretion. Finally, although hematocrit increases with SGLT2 inhibitors might favorably affect patients with coronary artery disease, in DAPA-HF, the benefit of dapagliflozin was similar in patients with or without an ischemic cardiomyopathy; furthermore, increases in hematocrit do not favorably affect the clinical course of patients with heart failure. Therefore, the results of DAPA-HF do not support many currently-held hypotheses about the mechanism of action of SGLT2 inhibitors in heart failure. Ongoing trials are likely to provide further insights.

scholarly journals Effects and Mechanisms of Tea for the Prevention and Management of Diabetes Mellitus and Diabetic Complications: An Updated Review

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 170 ◽  
Author(s):  
Jin-Ming Meng ◽  
Shi-Yu Cao ◽  
Xin-Lin Wei ◽  
Ren-You Gan ◽  
Yuan-Feng Wang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Experimental Studies ◽  
Epidemiological Studies ◽  
Mechanisms Of Action ◽  
Health Concern ◽  
High Morbidity ◽  
Protective Effects ◽  
Public Health Concern ◽  
Β Cells ◽  
Patients With Diabetes

Diabetes mellitus has become a serious and growing public health concern. It has high morbidity and mortality because of its complications, such as diabetic nephropathy, diabetic cardiovascular complication, diabetic neuropathy, diabetic retinopathy, and diabetic hepatopathy. Epidemiological studies revealed that the consumption of tea was inversely associated with the risk of diabetes mellitus and its complications. Experimental studies demonstrated that tea had protective effects against diabetes mellitus and its complications via several possible mechanisms, including enhancing insulin action, ameliorating insulin resistance, activating insulin signaling pathway, protecting islet β-cells, scavenging free radicals, and decreasing inflammation. Moreover, clinical trials also confirmed that tea intervention is effective in patients with diabetes mellitus and its complications. Therefore, in order to highlight the importance of tea in the prevention and management of diabetes mellitus and its complications, this article summarizes and discusses the effects of tea against diabetes mellitus and its complications based on the findings from epidemiological, experimental, and clinical studies, with the special attention paid to the mechanisms of action.

scholarly journals Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure

Heart ◽  
2021 ◽  
pp. heartjnl-2020-318060
Author(s):  
Shruti S Joshi ◽  
Trisha Singh ◽  
David E Newby ◽  
Jagdeep Singh
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Health ◽  
Blood Glucose Control ◽  
Sglt2 Inhibitor ◽  
Mechanisms Of Action ◽  
Calcium Handling ◽  
Healthy Population ◽  
Clinical Benefits

Patients with type 2 diabetes mellitus are at a higher risk of developing heart failure compared with the healthy population. In recent landmark clinical trials, sodium-glucose co-transporter 2 (SGLT2) inhibitor therapies improve blood glucose control and also reduce cardiovascular events and heart failure hospitalisations in patients with type 2 diabetes. Intriguingly, such clinical benefits have also been seen in patients with heart failure in the absence of type 2 diabetes although the underlying mechanisms are not clearly understood. Potential pathways include improved glycaemic control, diuresis, weight reduction and reduction in blood pressure, but none fully explain the observed improvements in clinical outcomes. More recently, novel mechanisms have been proposed to explain these benefits that include improved cardiomyocyte calcium handling, enhanced myocardial energetics, induced autophagy and reduced epicardial fat. We provide an up-to-date review of cardiac-specific SGLT2 inhibitor–mediated mechanisms and highlight studies currently underway investigating some of the proposed mechanisms of action in cardiovascular health and disease.

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