SGLT2 inhibitors: the statins of the 21st century

Braunwald, Eugene

doi:10.1093/eurheartj/ehab765

Cited by 59 publications

(58 citation statements)

References 13 publications

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“…Nevertheless, the above common features of coronary blood flow impairment in all forms of heart failure render them a valid target also for all established treatment strategies (statins, ACE inhibitors, AT1 blockers), but also a potential caveat (beta blockers: increased diastolic duration vs. increased vasoconstriction [ 86 , 95 ]) and a worthwhile target in the study of novel treatment options, e.g., neprilysin or sodium glucose transporter 2 (SGLT2) inhibition. [ 6 , 21 , 143 , 169 , 181 , 218 ].…”

Section: Conclusion and Directions For Future Researchmentioning

confidence: 99%

Coronary blood flow in heart failure: cause, consequence and bystander

Heusch

2022

Basic Res Cardiol

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Heart failure is a clinical syndrome where cardiac output is not sufficient to sustain adequate perfusion and normal bodily functions, initially during exercise and in more severe forms also at rest. The two most frequent forms are heart failure of ischemic origin and of non-ischemic origin. In heart failure of ischemic origin, reduced coronary blood flow is causal to cardiac contractile dysfunction, and this is true for stunned and hibernating myocardium, coronary microembolization, myocardial infarction and post-infarct remodeling, possibly also for the takotsubo syndrome. The most frequent form of non-ischemic heart failure is dilated cardiomyopathy, caused by genetic mutations, myocarditis, toxic agents or sustained tachyarrhythmias, where alterations in coronary blood flow result from and contribute to cardiac contractile dysfunction. Hypertrophic cardiomyopathy is caused by genetic mutations but can also result from increased pressure and volume overload (hypertension, valve disease). Heart failure with preserved ejection fraction is characterized by pronounced coronary microvascular dysfunction, the causal contribution of which is however not clear. The present review characterizes the alterations of coronary blood flow which are causes or consequences of heart failure in its different manifestations. Apart from any potentially accompanying coronary atherosclerosis, all heart failure entities share common features of impaired coronary blood flow, but to a different extent: enhanced extravascular compression, impaired nitric oxide-mediated, endothelium-dependent vasodilation and enhanced vasoconstriction to mediators of neurohumoral activation. Impaired coronary blood flow contributes to the progression of heart failure and is thus a valid target for established and novel treatment regimens.

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Section: Conclusion and Directions For Future Researchmentioning

confidence: 99%

Coronary blood flow in heart failure: cause, consequence and bystander

Heusch

2022

Basic Res Cardiol

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“…Despite the experimental differences among them, taken together, there are more studies in the bibliography supporting the increased expression levels of SGLT2 in diabetes than the contrary. Anyway, SGLT2 inhibition has been established as an effective therapeutic approach to treating T2DM and associated co-morbidities [ 10 ].…”

Section: Sglt1/2 Biologymentioning

confidence: 99%

“…However, despite most of them having been approved for their use in different countries, the exact mechanism through which they exert their actions besides glycosuria is not fully understood so far. Anyway, it seems clear that the development of SGLT2i has supposed a considerable improvement in the treatment of T2DM, heart failure, and diabetic renal disease [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models

Feijóo‐Bandín

Aragón-Herrera

Otero-Santiago

et al. 2022

IJMS

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Sodium-glucose co-transporter 2 inhibitors, also known as gliflozins, were developed as a novel class of anti-diabetic agents that promote glycosuria through the prevention of glucose reabsorption in the proximal tubule by sodium-glucose co-transporter 2. Beyond the regulation of glucose homeostasis, they resulted as being effective in different clinical trials in patients with heart failure, showing a strong cardio-renal protective effect in diabetic, but also in non-diabetic patients, which highlights the possible existence of other mechanisms through which gliflozins could be exerting their action. So far, different gliflozins have been approved for their therapeutic use in T2DM, heart failure, and diabetic kidney disease in different countries, all of them being diseases that have in common a deregulation of the inflammatory process associated with the pathology, which perpetuates and worsens the disease. This inflammatory deregulation has been observed in many other diseases, which led the scientific community to have a growing interest in the understanding of the biological processes that lead to or control inflammation deregulation in order to be able to identify potential therapeutic targets that could revert this situation and contribute to the amelioration of the disease. In this line, recent studies showed that gliflozins also act as an anti-inflammatory drug, and have been proposed as a useful strategy to treat other diseases linked to inflammation in addition to cardio-renal diseases, such as diabetes, obesity, atherosclerosis, or non-alcoholic fatty liver disease. In this work, we will review recent studies regarding the role of the main sodium-glucose co-transporter 2 inhibitors in the control of inflammation.

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“…In a reversal of the typical drug development timeline, translational research is playing catch up to explain the overwhelming clinical benefit of SGLT2i in CVOTs, and indeed much of the pleiotropic effects remain poorly explained [18].…”

Section: Proposed Mechanisms Of Action Of Sodiumglucose Cotransporter...mentioning

confidence: 99%

Seven suggestions for successful SGLT2i use in glomerular disease - a standalone CKD therapy?

McQuarrie

Gillis

Mark

2022

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewRecent advances in the world of glomerular diseases have largely focussed on remission induction with immune modulating therapy. It is well recognised that even with the best available treatments, patients with glomerular diseases may have an increased risk of progressive renal and cardiovascular disease. Recent findingsThe arrival of large trials looking at the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with chronic kidney disease (CKD) and diabetes or not has shifted the entire focus of current management and the shift needs to go further. This review summarises the background to these landmark trials and provides practical guidance for implementation of the results in a general nephrology clinic. In sub-group analyses of the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) clinical trial, SGLT2i improved renal outcomes in patients with immunoglobulin A (IgA) nephropathy highlighting the potential for this drug class in glomerular disease. We also discuss where the gaps in evidence are and where future trials in glomerular diseases, be they primary or secondary, should be focussed.

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SGLT2 inhibitors: the statins of the 21st century

Cited by 59 publications

References 13 publications

Coronary blood flow in heart failure: cause, consequence and bystander

Coronary blood flow in heart failure: cause, consequence and bystander

Role of Sodium-Glucose Co-Transporter 2 Inhibitors in the Regulation of Inflammatory Processes in Animal Models

Seven suggestions for successful SGLT2i use in glomerular disease - a standalone CKD therapy?

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