Modeling effects of <scp>SGLT</scp>‐2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes

Dziuba, Julia; Alperin, Peter; Racketa, Jill; Iloeje, Uchenna H.; Goswami, Devesh; Hardy, Elise; Perlstein, Itay; Grossman, Helene L.; Cohen, Marc

doi:10.1111/dom.12261

Cited by 93 publications

(64 citation statements)

References 32 publications

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“…Another recent meta-analysis has reported similar potential beneficial effect on CV outcomes of all SGLT2-I considered [61]. A simulated projection by using the Archimedes model showed that adding dapagliflozin to other antidiabetic agents further decreases CV and microvascular complications associated with T2DM over a 20-year period [62]. Thus, dapagliflozin has the potential for a beneficial effect both in the overall population and in those with a history of CV disease [8].…”

Section: Dapagliflozin and CV Riskmentioning

confidence: 88%

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

Avogaro

Giaccari

Fioretto

et al. 2017

Expert Review of Clinical Pharmacology

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Introduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin . Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inhibitors so far, the DECLARE trial, which will communicate whether this class of drugs will be disease-modifier in patients with type 2 diabetes also in primary prevention.

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Section: Dapagliflozin and CV Riskmentioning

confidence: 88%

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

Avogaro

Giaccari

Fioretto

et al. 2017

Expert Review of Clinical Pharmacology

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“…Recently, one study used the Archimedes Model to predict 20-year outcomes and found significant reductions in the risk of MI, stroke, CV death and all causes of death with SGLT2i treatment versus standard care. 166 Nevertheless, to confirm these results, several trials are now in progress in order to evaluate the CV safety of the other SGLT-2i. 150 The Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events (DECLARE-TIMI58), expected to be finished in 2019, was designed to evaluate the effect of dapagliflozin on the incidence of CV events.…”

Section: Cardiovascular Safety Of Sglt-2i: Evidence From Studiesmentioning

confidence: 97%

Cardiovascular safety of type 2 diabetes medications: Review of existing literature and clinical implications

Paredes¹,

Matta-Coelho²,

Monteiro³

et al. 2016

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Type 2 diabetes mellitus (T2DM), cardiovascular disease (CvD) and the cardiovascular effect of antidiabetic drugs are today critical medical issues, with the prevalence of T2DM in particular showing a steep increase worldwide, mainly due to unhealthy lifestyle habits. T2DM in association with obesity and other cardiovascular risk factors, results in the development of CvD, the leading cause of morbidity and mortality in patients with T2DM. Thus, treatment of T2DM is an individualized and complex challenge in which targeting cardiovascular risk factors is an important component in the decision making. given the cardiovascular adverse events associated with rosiglitazone, both the food and Drug Administration and the european Medicines Agency currently require the demonstration of cardiovascular safety of new antidiabetic drugs. Consequently, clinical trials to guarantee their cardiovascular safety are now obligatory. This review aims to summarize the available evidence on the cardiovascular effects and safety of the major drugs used in T2DM treatment and also to provide an overview of upcoming and ongoing clinical trials in this field. Our belief is that this review will be of substantial assistance to all medical doctors who are treating diabetic patients, namely primary care physicians, internal medicine doctors, endocrinologists, diabetologists and less well experienced personnel such as young doctors in training.

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“…However, a recent study on dapagliflozin proposed that SGLT-2 inhibitors may possess an additional diuretic-like capacity to lower blood pressure [173]. The improvements in blood pressure, associated to a moderate decrease in body weight [174] induced by treatment with SGLT-2 inhibitors suggest the potential for reducing the risk of cardiovascular events [175,176]. To date, SGLT-2 inhibitors are generally well tolerated, with a favorable safety profile similar to that of placebo.…”

Section: How Conventional Diabetic Treatments May Ameliorate Endothelmentioning

confidence: 99%

“…The epigallocatechin-3-gallate (EGCG), the most abundant active polyphenolic component of green tea, is capable of inhibiting NLRP3 inflammasome via enhancing the Nrf2 antioxidant pathway [184]. Moreover, the protective effects of astragaloside IV and cycloastragenol -both contained in Astragalus membranaceus Moench (Fabaceae) -against endoplasmic reticulum stress-induced apoptosis are thought to be mediated via NLRP3 inflammasome inhibition in endothelial cells [176,185]. NLRP3 inflammasome inhibition has also been proposed as new pivotal mechanism contributing to endothelial protective function of rutin, a flavonoid that can be obtained from different dietary sources [186].…”

Section: New Strategies For Treatment Of Diabetes and Their Impact Onmentioning

confidence: 99%

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

Potenza

Nacci

Salvia

et al. 2017

Pharmacological Research

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Abstract:The association of obesity and diabetes, termed "diabesity", defines a combination of primarily metabolic disorders with insulin resistance as the underlying common pathophysiology. Cardiovascular disorders associated with diabesity represent the leading cause of morbidity and mortality in the Western world. This makes diabesity, with its rising impacts on both health and economics, one of the most challenging biomedical and social threats of present century. The emerging comprehension of the genes whose alteration confers inter-individual differences on risk factors for diabetes or obesity, together with the potential role of genetically determined variants on mechanisms controlling responsiveness, effectiveness and safety of anti-diabetic therapy underlines the need of additional knowledge on molecular mechanisms involved in the pathophysiology of diabesity. Endothelial cell dysfunction, resulting from the unbalanced production of endothelialderived vascular mediators, is known to be present at the earliest stages of insulin resistance and obesity, and may precede the clinical diagnosis of diabetes by several years. Once considered as a mere consequence of metabolic abnormalities, it is now clear that endothelial dysfunctional activity may play a pivotal role in the progression of diabesity. In the vicious circle where vascular defects and metabolic disturbances worsen and reinforce each other, a low-grade, chronic, and 'cold' inflammation (metaflammation) has been suggested to serve as the pathophysiological link that binds endothelial and metabolic dysfunctions. In this paradigm, it is important to consider how traditional antidiabetic treatments (specifically addressing metabolic dysregulation) may directly impact on inflammatory processes or cardiovascular function. Indeed, not all drugs currently available to treat diabetes possess the same anti-inflammatory potential, or target endothelial cell function equally. Perspective strategies pointing at reducing metaflammation or directly addressing endothelial dysfunction may disclose beneficial consequences on metabolic regulation. This review focuses on existing and potential new approaches ameliorating endothelial dysfunction and vascular inflammation in the context of diabesity.

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Modeling effects of SGLT‐2 inhibitor dapagliflozin treatment versus standard diabetes therapy on cardiovascular and microvascular outcomes

Abstract: On the basis of simulation results, adding dapagliflozin to currently available treatment options is projected to further decrease the CV and microvascular complications associated with T2DM.

Cited by 93 publications

References 32 publications

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

Cardiovascular safety of type 2 diabetes medications: Review of existing literature and clinical implications

Targeting endothelial metaflammation to counteract diabesity cardiovascular risk: Current and perspective therapeutic options

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