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https://www.readbyqxmd.com/read/29197997/class-effects-of-sglt2-inhibitors-in-mouse-cardiomyocytes-and-hearts-inhibition-of-na-h-exchanger-lowering-of-cytosolic-na-and-vasodilation
#1
Laween Uthman, Antonius Baartscheer, Boris Bleijlevens, Cees A Schumacher, Jan W T Fiolet, Anneke Koeman, Milena Jancev, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic Na+ ([Na+]c) and cytosolic Ca2+ ([Ca2+]c) concentrations through inhibition of Na+/H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+]c; (2) a structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i affect the haemodynamic and metabolic performance of isolated hearts of healthy mice...
December 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/29196150/sglt2-inhibitors-with-cardiovascular-benefits-transforming-clinical-care-in-type2-diabetes-mellitus
#2
REVIEW
Michael d'Emden, John Amerena, Gary Deed, Carol Pollock, Mark E Cooper
Cardiovascular risk reduction in individuals with Type 2 diabetes mellitus (T2DM) is a key part of clinical management. Sodium-glucose co-transporter (SGLT2) inhibitors improve glycaemic control, reduce body weight and decrease blood pressure. In addition, the SGLT2 inhibitors empagliflozin and canagliflozin reduced the risk of composite cardiovascular events in high-risk individuals with T2DM in the EMPA-REG OUTCOME trial and the CANVAS Program, respectively. Empagliflozin also reduced cardiovascular deaths and improved renal outcomes...
November 28, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29186300/un-sweetening-the-heart-possible-pleiotropic-effects-of-sglt2-inhibitors-on-cardio-and-cerebrovascular-alterations-in-resistant-hypertensive-subjects
#3
Mariana R Pioli, Alessandra M V Ritter, Rodrigo Modolo
Resistant hypertension is a multifactorial disease associated with several target organ damage, such as microalbuminuria, left ventricular hypertrophy and arterial stiffness. These subjects have high cardiovascular complications, especially when associated with diabetes condition. SGLT-2 inhibitors represent a new class of oral antidiabetic drugs that have shown positive effects in diabetics and even hypertensives subjects. Several studies demonstrated positive outcomes related to blood pressure levels, body weight and glycemic control...
November 23, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#4
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29140125/diabetes-area-patent-participation-analysis-part-ii-years-2011-2016
#5
Markus Boehm, Matthew Crawford, Jamie E Moscovitz, Philip A Carpino
Diabetes is a metabolic disease characterized by elevated levels of plasma glucose. When untreated, diabetes increases the risk of developing co-morbidities such as cardiovascular disease. Several drugs, often used as part of combination therapies, have been approved to treat the disease, but these drugs will eventually fail to effectively control blood glucose levels, at which point insulin replacement therapy is required. A medical need exists for new anti-diabetic drugs that exhibit good efficacy with improved safety/toleration profiles and can be added on top of existing therapies, or that can provide additional benefits beyond glucose lowering such as pancreatic beta (β)-cell protection...
November 15, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29127757/-gliflozins-slow-down-the-progression-of-diabetic-kidney-disease
#6
Vladimír Tesař, Jan Vachek
Until recently progression of diabetic kidney disease could have been slowed down only by the inhibition of the renin-angiotensin system. Inhibitors of SGLT2 (sodium-glucose transporter 2) in the proximal tubulus of the kidney induce natriuresis and by the activation of the tubuloglomerular feedback increase the tone of the afferent arteriole and decrease the glomerular pressure. Empagliflozin in the study EMPA-REG Outcome significantly decreased the risk of progression of diabetic kidney disease and further analyses also demonstrated its potent antiproteinuric effect...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29094264/treating-disease-mechanisms-in-patients-with-heart-failure-and-diabetes-mellitus
#7
REVIEW
Amanda Trang, David Aguilar
PURPOSE OF REVIEW: Diabetes and heart failure commonly coexist and portend worsened prognosis than either disease alone. We explore mechanisms that may serve as potential treatment targets and review the effects of various contemporary glucose-lowering agents on heart failure outcomes. RECENT FINDINGS: Promising data has emerged on sodium-glucose cotransporter 2 (SLGT2) inhibitors as the first class of agents to improve cardiovascular mortality and heart failure outcomes in diabetic individuals both with and without established heart failure...
December 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/29076040/sglt2-inhibitors-through-the-windows-of-empa-reg-and-canvas-trials-a-review
#8
REVIEW
Ashu Rastogi, Anil Bhansali
EMPA-REG OUTCOME and CANVAS trials were designed to study the cardiovascular safety of empagliflozin and canagliflozin, respectively. Both studies were sufficiently powered to study the non-inferiority for cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (DM) and showed superiority for major adverse cardiovascular events and composite renal outcomes independent of glycemic control. Further, all patients in EMPA-REG had prior CV events (secondary prevention), compared to CANVAS that also included subjects with no prior CV events, indicating the beneficial effects of canagliflozin in primary prevention of CV events as well...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29063276/the-infamous-famous-sulfonylureas-and-cardiovascular-safety-much-ado-about-nothing
#9
REVIEW
Laurentiu M Pop, Ildiko Lingvay
PURPOSE OF REVIEW: Sulfonylureas (SUs) are one of the most commonly used glucose-lowering agents worldwide. While their efficacy is undisputed, their cardiovascular safety has been debated since the 1970's. RECENT FINDINGS: With no dedicated cardiovascular studies to definitively answer this question, observational studies and meta-analyses abound and have reported divergent results, fueling the controversy. Studies that compared SUs to metformin or newer agents, like GLP-1 agonists and SGLT2 inhibitors, suggest a difference in cardiovascular events, yet this is likely the result of beneficial effects of the latter...
October 23, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/29061576/sodium-glucose-cotransporter-2-inhibition-in-heart-failure-potential-mechanisms-clinical-applications-and-summary-of-clinical-trials
#10
REVIEW
Yuliya Lytvyn, Petter Bjornstad, Jacob A Udell, Julie A Lovshin, David Z I Cherney
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 ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor...
October 24, 2017: Circulation
https://www.readbyqxmd.com/read/29042751/spotlight-on-ertugliflozin-and-its-potential-in-the-treatment-of-type-2-diabetes-evidence-to-date
#11
REVIEW
Francesca Cinti, Simona Moffa, Flavia Impronta, Chiara Ma Cefalo, Vinsin A Sun, Gian Pio Sorice, Teresa Mezza, Andrea Giaccari
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the latest therapeutic strategy in the treatment of type 2 diabetes mellitus (T2DM). Using an insulin-independent mechanism (glycosuria), they reduce glucose toxicity and improve insulin sensitivity and β-cell function. The promising results obtained in clinical trials show that SGLT2 significantly improves glycemic control and provides greater cardiovascular protection, combined with a reduction in body weight and blood pressure (BP). This review focuses on ertugliflozin, a new, highly selective, and reversible SGLT2 inhibitor...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29042392/renal-and-cardiovascular-effects-of-sodium-glucose-cotransporter-2-sglt2-inhibition-in-combination-with-loop-diuretics-in-diabetic-patients-with-chronic-heart-failure-recede-chf-protocol-for-a-randomised-controlled-double-blind-cross-over-trial
#12
Natalie A Mordi, Ify R Mordi, Jagdeep S Singh, Fatima Baig, Anna-Maria Choy, Rory J McCrimmon, Allan D Struthers, Chim C Lang
INTRODUCTION: Type 2 diabetes (T2D) and heart failure (HF) are a frequent combination, where treatment options remain limited. There has been increasing interest around the sodium-glucose cotransporter 2 (SGLT2) inhibitors and their use in patients with HF. Data on the effect of SGLT2 inhibitor use with diuretics are limited. We hypothesise that SGLT2 inhibition may augment the effects of loop diuretics and the benefits of SGLT2 inhibitors may extend beyond those of their metabolic (glycaemic parameters and weight loss) and haemodynamic parameters...
October 16, 2017: BMJ Open
https://www.readbyqxmd.com/read/29039237/sglt2-inhibitors-are-they-safe
#13
Sebastian Filippas-Ntekouan, Theodosios D Filippatos, Moses S Elisaf
Sodium-glucose linked transporter type 2 (SGLT2) inhibitors are a relatively new class of antidiabetic drugs with positive cardiovascular and kidney effects. The aim of this review is to present the safety issues associated with SGLT2 inhibitors. Urogenital infections are the most frequently encountered adverse events, although tend to be mild to moderate and are easily manageable with standard treatment. Although no increased acute kidney injury risk was evident in the major trials, the mechanism of action of these drugs requires caution when they are administered in patients with extracellular volume depletion or with drugs affecting renal hemodynamics...
October 27, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/29030201/sglt2-inhibitors-hypotheses-on-the-mechanism-of-cardiovascular-protection
#14
Robert M Bell, Derek M Yellon
No abstract text is available yet for this article.
October 10, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/29025406/impact-of-empagliflozin-on-subclinical-left-ventricular-dysfunctions-and-on-the-mechanisms-involved-in-myocardial-disease-progression-in-type-2-diabetes-rationale-and-design-of-the-empa-heart-trial
#15
Andrea Natali, Lorenzo Nesti, Iacopo Fabiani, Enrico Calogero, Vitantonio Di Bello
BACKGROUND: Asymptomatic left ventricular (LV) dysfunction is highly prevalent in type 2 diabetes patients. Unlike the other hypoglycemic drugs, SGLT2 inhibitors have shown potential benefits for reducing cardiovascular death and risk factors, aside from lowering plasma glucose levels. With this study we aim at determining whether the treatment with empagliflozin is associated with an improvement in LV functions in diabetic patients with asymptomatic LV dysfunction against Sitagliptin, which is presumably neutral on myocardial function...
October 12, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29016751/cardiac-effects-of-sglt2-inhibitors-the-sodium-hypothesis
#16
Edoardo Bertero, Leticia Prates Roma, Pietro Ameri, Christoph Maack
The effects of intense glycaemic control on macrovascular complications in patients with type 2 diabetes are incompletely resolved, and many glucose-lowering medications negatively affect cardiovascular outcomes. Recently, the EMPA-REG OUTCOME trial revealed that empagliflozin, an inhibitor of the sodium-glucose cotransporter 2 (SGLT2), substantially reduced the risk of hospitalization for heart failure, death from cardiovascular causes, and all-cause mortality in patients with type 2 diabetes mellitus at high cardiovascular risk...
August 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29016744/novel-effects-of-dapagliflozin-on-epicardial-adipose-tissue-with-insulin-resistance-high-levels-of-inflammatory-chemokines-production-and-low-differentiation-ability
#17
Esther Díaz-Rodríguez, Rosa M Agra, Ángel L Fernández, B Adrio, Tomás García-Caballero, José R González-Juanatey, Sonia Eiras
Aims: In patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, high pro-inflammatory chemokines and low differentiation ability. Since dapagliflozin reduces body fat and cardiovascular events in diabetic patients, we wanted to know its effect on EAT and subcutaneous adipose tissue (SAT). Methods and results: Adipose samples were obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter 2 (SGLT2) expression was determined by real time PCR (n = 20), Western blot and immunohistochemistry...
September 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28978622/sglt2-inhibitors-and-cardiovascular-outcomes
#18
(no author information available yet)
No abstract text is available yet for this article.
October 4, 2017: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/28952138/can-sglt2-inhibitors-cause-acute-renal-failure-plausible-role-for-altered-glomerular-hemodynamics-and-medullary-hypoxia
#19
REVIEW
Auryan Szalat, Amichai Perlman, Mordechai Muszkat, Mogher Khamaisi, Zaid Abassi, Samuel N Heyman
Sodium-glucose co-transporter-2 inhibitors (SGLT2i) provide outstanding long-term cardiovascular and renal protection in high-risk patients with type 2 diabetes mellitus. Yet, despite encouraging renal safety outcomes reported in the EMPA-REG study, scattered reports suggest that there might be a risk for acute kidney injury (AKI), which may occasionally be fatal or might require renal replacement therapy. Reduced trans-glomerular pressure with a modest decline in kidney function, an inherent characteristic of SGLT2i therapy, conceivably forms the basis for the long-term renal protection, resembling agents that block the renin-angiotensin-aldosterone (RAAS) axis...
September 26, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28942789/the-role-of-sodium-glucose-cotransporter-2-inhibitors-in-the-management-of-type-2-diabetes
#20
REVIEW
Oren Steen, Ronald M Goldenberg
Sodium-glucose cotransporter 2 (SGTL2) inhibitors are a novel class of antihyperglycemic agents that work in an insulin-independent manner by promoting urinary glucose excretion. In addition to efficacious glucose lowering, they exert beneficial effects on blood pressure and weight while avoiding hypoglycemia unless combined with insulin or insulin secretagogues. This review explores the mechanism of action of SGLT2 inhibitors, their effects on glycated hemoglobin, weight, blood pressure and hypoglycemia, potential adverse effects, renal considerations and cardiovascular outcomes...
October 2017: Canadian Journal of Diabetes
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