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Empagliflozin

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https://www.readbyqxmd.com/read/29203583/how-does-empagliflozin-reduce-cardiovascular-mortality-insights-from-a-mediation-analysis-of-the-empa-reg-outcome-trial
#1
Silvio E Inzucchi, Bernard Zinman, David Fitchett, Christoph Wanner, Ele Ferrannini, Martin Schumacher, Claudia Schmoor, Kristin Ohneberg, Odd Erik Johansen, Jyothis T George, Stefan Hantel, Erich Bluhmki, John M Lachin
OBJECTIVE: In the EMPA-REG OUTCOME trial involving 7,020 patients with type 2 diabetes and established cardiovascular (CV) disease, empagliflozin given in addition to standard of care reduced the risk of CV death by 38% versus placebo (hazard ratio [HR] 0.62 [95% CI 0.49, 0.77]). This exploratory mediation analysis assesses the extent to which treatment group differences in covariates during the trial contributed to CV death risk reduction with empagliflozin. RESEARCH DESIGN AND METHODS: Effects of potential mediators, identified post hoc, on the HR for CV death with empagliflozin versus placebo were analyzed by Cox regression models, with treatment group adjusted for the baseline value of the variable and its change from baseline or updated mean (i...
December 4, 2017: Diabetes Care
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
#2
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
#3
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/29193767/empagliflozin-decreases-remnant-like-particle-cholesterol-in-type2-diabetic-patients-with-insulin-resistance
#4
Sachiko Hattori
AIMS/INTRODUCTION: Remnant lipoproteins are thought to be atherogenic. Remnant-like particle cholesterol (RLP-C), which reflects the levels of various kinds of remnant lipoproteins in the blood, has a significant correlation with insulin resistance. MATERIALS AND METHODS: In this study, we measured the effect of empagliflozin (EMPA) on the levels of RLP-C and investigated whether EMPA-mediated change in RLP-C is associated with a change in insulin resistance in type2 diabetic patients who have insulin resistance...
November 28, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/29183654/-safety-of-sglt2-inhibitors-a-review-of-the-adverse-drug-reactions-registered-in-a-national-database
#5
O Esteban-Jiménez, C Navarro-Pemán, L Urieta-González
OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26...
November 25, 2017: Semergen
https://www.readbyqxmd.com/read/29174031/acute-renal-failure-with-sodium-glucose-cotransporter-2-inhibitors-analysis-of-the-fda-adverse-event-report-system-database
#6
A Perlman, S N Heyman, I Matok, J Stokar, M Muszkat, A Szalat
BACKGROUND AND AIMS: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. METHODS AND RESULTS: We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016...
October 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29168387/impacts-of-sodium-glucose-co-transporter-type-2-inhibitors-on-central-blood-pressure
#7
Tsuneo Takenaka, Yoichi Ohno, Hiromichi Suzuki
AIMS: To assess the effects of sodium-glucose co-transporter type 2 inhibitors on central blood pressure, an important determinant of cardiovascular events. METHODS: Canagliflozin, Empagliflozin or Luseogliflozin was given for 102 type 2 diabetic patients with hypertension and nephropathy. Central blood pressure was evaluated by radial tonometry. Clinical parameters were followed for 6 months. RESULTS: Three differing sodium-glucose co-transporter type 2 inhibitors similarly reduced brachial and central blood pressures, casual blood sugar, haemoglobin A1c, estimated glomerular filtration rate and albuminuria without significant changes in pulse rate and lipid profiles...
November 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/29165885/the-association-between-the-dosage-of-sglt2-inhibitor-and-weight-reduction-in-type-2-diabetes-patients-a-meta-analysis
#8
Xiaoling Cai, Wenjia Yang, Xueying Gao, Yifei Chen, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors. METHODS: Overall, 55 placebo-controlled trials were included. RESULTS: The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1...
November 22, 2017: Obesity
https://www.readbyqxmd.com/read/29157870/cost-utility-of-empagliflozin-in-patients-with-type-2-diabetes-at-high-cardiovascular-risk
#9
Elaine Nguyen, Craig I Coleman, Suresh Nair, Erin R Weeda
AIMS: In the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG) trial, empagliflozin reduced cardiovascular and all-cause mortality in type 2 diabetes (T2D) patients at high cardiovascular risk. We sought to estimate the cost-effectiveness of empagliflozin versus standard treatment for the prevention of cardiovascular morbidity and mortality in patients with T2D. METHODS: A Markov model was developed to assess the cost-effectiveness of empagliflozin (versus standard treatment) for the prevention of cardiovascular morbidity and mortality in patients with T2D using a 3-month cycle length and a lifetime horizon...
October 14, 2017: Journal of Diabetes and its Complications
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
#10
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/29139301/design-of-a-24-week-trial-of-empagliflozin-once-daily-in-hypertensive-black-african-american-patients-with-type-2-diabetes-mellitus
#11
Keith C Ferdinand, Leo Seman, Afshin Salsali
OBJECTIVE: Black/African American patients have higher prevalence of type 2 diabetes mellitus (T2DM), diabetes-related complications, and hypertension, but they are often underrepresented in clinical trials. The sodium-glucose co-transporter 2 inhibitor, empagliflozin, was associated with significant improvements in glucose control (via hemoglobin [Hb] A1c) and reductions in blood pressure (BP; via office and ambulatory BP monitoring) in a primarily white population with T2DM and hypertension...
November 15, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29133603/canagliflozin-cui-bono
#12
Matthew A Cavender, Mikhail Kosiborod
Cardiovascular disease accounts for the majority of excess deaths seen in patients with Type 2 diabetes (T2D).(1) Thus, in order to improve outcomes in this population, clinicians should focus on therapies that decrease the risk of subsequent cardiovascular events. Over the last two years, randomized controlled clinical trials have identified several agents that decrease cardiovascular events in patients with T2D with or at high risk for cardiovascular disease (CVD) - effects likely unrelated to glucose-lowering, the indication for which they were originally developed...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29133602/cardiovascular-outcomes-and-safety-of-empagliflozin-in-patients-with-type-2-diabetes-mellitus-and-peripheral-artery-disease-a-subanalysis-of-empa-reg-outcome
#13
Subodh Verma, C David Mazer, Mohammed Al-Omran, Silvio E Inzucchi, David Fitchett, Uwe Hehnke, Jyothis T George, Bernard Zinman
Peripheral artery disease (PAD) is one of the most common cardiovascular complications in patients with type 2 diabetes mellitus (T2DM)(1) and is a predictor of cardiovascular death.(2) Interventions that reduce cardiovascular complications in this patient population are urgently required. In the EMPA-REG OUTCOME trial, the sodium glucose cotransporter 2 inhibitor empagliflozin reduced the risk of cardiovascular death by 38% (hazard ratio [HR], 0.62; 95% confidence interval [CI] 0.49-0.77]) and hospitalization for heart failure (HHF) by 35% (HR, 0...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29130831/a-predominant-oxidative-renal-metabolite-of-empagliflozin-in-male-mice-is-cytotoxic-in-mouse-renal-tubular-cells-but-not-genotoxic
#14
James D Smith, Zimei Huang, Patricia A Escobar, Pamela Foppiano, Hlaing Maw, William Loging, Hongbin Yu, Jonathan A Phillips, Mitchell Taub, Warren W Ku
In a previously reported CD-1 mouse 2-year carcinogenicity study with the sodium glucose cotransporter-2 inhibitor empagliflozin, an increased incidence of renal tubular adenomas and carcinomas was identified only in the male high-dose group. Follow-up investigative studies have shown that the renal tumors in male high-dose mice were preceded by a number of renal degenerative/regenerative findings. Prior cross-species in vitro metabolism studies using microsomes identified an oxidative metabolite (M466/2) predominantly formed in the male mouse kidney and which spontaneously degrades to a metabolite (M380/1) and reactive 4-OH crotonaldehyde (CTA)...
January 1, 2017: International Journal of Toxicology
https://www.readbyqxmd.com/read/29127757/-gliflozins-slow-down-the-progression-of-diabetic-kidney-disease
#15
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/29101501/severe-hypernatraemic-dehydration-and-unconsciousness-in-a-care-dependent-inpatient-treated-with-empagliflozin
#16
Georg Gelbenegger, Nina Buchtele, Christian Schoergenhofer, Martin Roeggla, Michael Schwameis
A 66-year-old Caucasian male became unconscious 2 weeks after initiation of add-on therapy with empagliflozin for poorly controlled type 2 diabetes mellitus. The inpatient had recently suffered focal pontine stroke, rendering him bedridden and requiring increased nursing care, including assistance with drinking. The patient had received empagliflozin 10 mg once daily for glycaemic control. Investigations revealed hypernatraemia (164 mmol/l), a urine glucose level of 3935 mg/dl, and a creatinine level of 2...
November 3, 2017: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/29084249/the-effect-of-sodium-glucose-cotransporter-2-sglt2-inhibition-on-the-urinary-proteome
#17
David Cherney, Bruce A Perkins, Yuliya Lytvyn, Hiddo Heerspink, María E Rodríguez-Ortiz, Harald Mischak
Treatment with empagliflozin, an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), is associated with slower progression of diabetic kidney disease. In this analysis, we explored the hypothesis that empagliflozin may have an impact on urinary peptides associated with chronic kidney disease (CKD). In this post-hoc, exploratory analysis, we investigated urine samples obtained from 40 patients with uncomplicated type 1 diabetes (T1D) before and after treatment with empagliflozin for 8 weeks to for significant post-therapy changes in urinary peptides...
2017: PloS One
https://www.readbyqxmd.com/read/29076040/sglt2-inhibitors-through-the-windows-of-empa-reg-and-canvas-trials-a-review
#18
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/29061576/sodium-glucose-cotransporter-2-inhibition-in-heart-failure-potential-mechanisms-clinical-applications-and-summary-of-clinical-trials
#19
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/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
#20
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
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