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https://www.readbyqxmd.com/read/27903028/-cardiovascular-morbidity-and-mortality-in-patients-with-kidney-disease
#1
Ivo Quack, Ralf Westenfeld
Patients with kidney disease have a significantly increased cardiovascular morbidity and mortality. Especially diabetics have an increased risk to develop renal insufficiency and cardiovascular events. Two recent studies show that the SGLT2 inhibitor Empagliflozin and the GLP1 agonist Liraglutid are able to lower the cardiovascular risk of type2 diabetics with renal insufficiency. Recent observations suggest that bradycardia and asystole are main triggers for sudden cardiac death in patients with chronic kidney disease...
November 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27898586/an-update-on-sodium-glucose-co-transporter-2-inhibitors-for-the-treatment-of-diabetes-mellitus
#2
Daniel S Hsia, Owen Grove, William T Cefalu
PURPOSE OF REVIEW: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are the newest class of oral antihyperglycemic agents that have been approved for the treatment of diabetes mellitus. Over the past year, there have been significant developments in both the safety and efficacy of this class of medications that are presented in this review. RECENT FINDINGS: Apart from data on the glucose-lowering effect of SGLT2 inhibitors, other metabolic benefits have been demonstrated for this class of medications...
November 24, 2016: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/27894216/bone-effects-of-canagliflozin-a-sodium-glucose-co-transporter-2-inhibitor-in-patients-with-type-2-diabetes-mellitus
#3
Thomas C Blevins, Azeez Farooki
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor approved for the treatment of type 2 diabetes mellitus (T2DM), lowers blood glucose by inhibiting renal glucose reabsorption and increasing urinary glucose excretion. It has been reported that SGLT2 inhibitors may have potential adverse effects on bone, including increased fracture risk and decreased bone mineral density (BMD). Across clinical studies, canagliflozin was not associated with meaningful changes in serum or urine calcium, vitamin D, or parathyroid hormone...
November 28, 2016: Postgraduate Medicine
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#4
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
November 22, 2016: Diabetologia
https://www.readbyqxmd.com/read/27867961/cardio-renal-protection-with-empagliflozin
#5
Richard J MacIsaac, George Jerums, Elif I Ekinci
Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27866701/place-of-sodium-glucose-cotransporter-2-inhibitors-in-east-asian-subjects-with-type-2-diabetes-mellitus-insights-into-the-management-of-asian-phenotype
#6
REVIEW
Lee Ling Lim, Alexander Tong Boon Tan, Kevin Moses, Viraj Rajadhyaksha, Siew Pheng Chan
The burden of type 2 diabetes (T2DM) in East Asia is alarming. Rapid modernization and urbanization have led to major lifestyle changes and a tremendous increase in the prevalence of obesity, metabolic syndrome, and diabetes mellitus. The development of T2DM at a younger age, with lower body mass index, higher visceral adiposity, and more significant pancreatic beta-cell dysfunction compared to Caucasians are factors responsible for the increased prevalence of T2DM in East Asians. Sodium-glucose Cotransporter-2 (SGLT2) inhibitors (canagliflozin, dapaglifozin, empagliflozin, etc...
October 15, 2016: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/27866224/the-beneficial-effects-of-empagliflozin-an-sglt2-inhibitor-on-atherosclerosis-in-apoe-mice-fed-a-western-diet
#7
Ji Hye Han, Tae Jung Oh, Ghayoung Lee, Hyo Jin Maeng, Dong Hwa Lee, Kyoung Min Kim, Sung Hee Choi, Hak Chul Jang, Hye Seung Lee, Kyong Soo Park, Young-Bum Kim, Soo Lim
AIMS/HYPOTHESIS: A recent large clinical study has shown that empagliflozin has a lower rate of cardiovascular and all-cause mortality when compared with placebo in patients with type 2 diabetes. We investigated the effect of empagliflozin (compared with glimepiride) on the progression of atherosclerosis, and its possible mechanisms of action. METHODS: Forty-eight 5-week-old male ApoE (-/-) mice were fed a western diet for 20 weeks and divided into four groups: control (saline, 154 mmol/l NaCl), glimepiride 0...
November 19, 2016: Diabetologia
https://www.readbyqxmd.com/read/27865185/a-new-era-in-the-management-of-type-2-diabetes-is-cardioprotection-at-long-last-a-reality
#8
EDITORIAL
Xavier Rossello, Derek M Yellon
The EMPA-REG OUTCOME and the LEADER trials have revealed a new era in the management of type 2 diabetes. The SGLT2 inhibitor empagliflozin demonstrated a lower rate of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke compared to placebo. Liraglutide, a GLP-1 analogue, succeeded to demonstrate reduction on a composite outcome including first occurrence of cardiovascular death, nonfatal myocardial infarction or non-fatal stroke. These two medications act through different mechanisms and has consequently shown different patterns of cardiovascular benefit...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27829948/increased-hematocrit-during-sodium-glucose-cotransporter-2-inhibitor-therapy-indicates-recovery-of-tubulointerstitial-function-in-diabetic-kidneys
#9
REVIEW
Motoaki Sano, Makoto Takei, Yasuyuki Shiraishi, Yoshihiko Suzuki
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been attracting attention for cardiovascular as well as antidiabetic effects since the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME Trial) were reported. The hematocrit increases during treatment with SGLT2 inhibitors, which have a diuretic effect but do not cause sufficient hemoconcentration to increase the risk of cerebral infarction. Elevation of the hematocrit during SGLT2 inhibitor therapy is presumed to involve enhancement of erythropoiesis in addition to hemoconcentration...
December 2016: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/27819144/effects-of-sodium-glucose-co-transporter-2-inhibitors-on-metabolism-unanswered-questions-and-controversies
#10
Vasilios Tsimihodimos, Theodosios D Filippatos, Moses S Elisaf
Sodium-glucose co-transporter 2 (SGLT2) inhibitors inhibit glucose re-absorption in the proximal renal tubules. These drugs also affect many anthropometric and metabolic parameters with various mechanisms of action. Areas covered: We present the available evidence regarding these effects. SGLT2 inhibitors can decrease body weight mainly due to a reduction of total fat mass. SGLT2 inhibitors can decrease blood pressure levels and serum uric acid levels and may also reduce the degree of diabetes-related albuminuria...
November 17, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27817207/evaluation-of-the-pharmacokinetics-pharmacodynamics-and-clinical-efficacy-of-empagliflozin-for-the-treatment-of-type-2-diabetes
#11
Brian Tomlinson, Miao Hu, Yuzhen Zhang, Paul Chan, Zhong-Min Liu
Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest class of drugs to be introduced for the treatment of type 2 diabetes mellitus. These drugs improve glycemic control by increasing urinary glucose excretion and exert additional benefits of weight loss and blood pressure reductions. Areas covered: This review outlines the background to SGLT2 inhibitors and provides details on the pharmacokinetics, pharmacodynamics and clinical efficacy of empagliflozin and discusses the cardiovascular outcome trial...
November 20, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27812962/implications-of-the-empa-reg-trial-for-clinical-care-and-research
#12
REVIEW
Angeliki M Stamatouli, Silvio E Inzucchi
EMPA-REG OUTCOME was a multicenter, randomized placebo-controlled trial that examined the effect of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor in addition to standard of care in patients with type 2 diabetes and established cardiovascular (CV) disease. The primary goal was to assess CV safety, as mandated by the US Food and Drug Administration since 2008 for all new glucose-lowering agents. Secondary goals were to examine the effects of empagliflozin on microvascular outcomes and, in particular, kidney disease...
December 2016: Current Diabetes Reports
https://www.readbyqxmd.com/read/27776917/which-is-the-main-molecular-target-responsible-for-the-cardiovascular-benefits-in-the-empa-reg-outcome-trial-a-journey-through-the-kidney-the-heart-and-other-interesting-places
#13
REVIEW
M Luconi, L Raimondi, A Di Franco, E Mannucci
BACKGROUND: The results of the EMPA-REG-OUTCOME trial on type 2 diabetic patients at high risk for prior cardiovascular events showed that empagliflozin produces a remarkable reduction in the rates of hospitalization for heart failure (35%), cardiovascular death (38%), and all-cause death (32%). This unexpected cardio-protective action cannot be accounted for by the improvement of "classical" cardiovascular risk factors. AIMS: This review aims at summarizing current knowledge on the cardiovascular action of SGLT2 inhibitors and discuss the different hypotheses formulated to explain the results of the EMPA-REG-OUTCOME-study...
December 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27754289/br-08-1-high-sodium-intake-reduction-in-diabetes-with-hypertension
#14
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27754220/os-32-05-effects-of-sglt2-inhibitors-on-circadian-rhythm-of-blood-pressure-in-rats
#15
Asadur Rahman, Yui Takeshige, Yoshihide Fujisawa, Hirofumi Hitomi, Daisuke Nakano, Akira Nishiyama
OBJECTIVE: Disrupted circadian rhythm of blood pressure is associated with cardiovascular events in metabolic syndrome and obesity. Experiments were conducted to examine the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on circadian rhythm of blood pressure in a genetic model of obese metabolic syndrome (SHR/NDmcr-cp (+/+) (SHRcp)) and salt-treated obese Otsuka Long Evans Tokushima Fatty (OLETF) rats. DESIGN AND METHOD: Luseogliflozin (10 mg/kg/day, p...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753989/sy-10-3-sglt2-inhibitors-as-potential-antihypertensive-and-renoprotective-agents
#16
Peter Mertens
Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. The new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753988/sy-10-2-the-role-of-sglt2-inhibitors-in-the-management-of-t2dm
#17
Chang Hee Jung
Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder and is a major global public health problem with a rapidly increasing prevalence. Although a wide range of pharmacotherapy for glycemic control in T2DM is now available, management of T2DM remains complex and challenging. The kidneys contribute to glucose homeostasis primarily by the glucose reabsorption from the glomerular filtrate. The sodium-glucose co-transporter 2 (SGLT2) inhibitors, a new class of antidiabetes agents that inhibit glucose absorption from the kidney tubule independent of insulin, offer a unique opportunity to improve outcomes for patient with T2DM...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753929/os-05-04-empagliflozin-exerts-cardio-and-nephro-protective-effects-in-cohen-rosenthal-diabetic-hypertensive-rats
#18
Zaid Abassi, Jonatan Leor, Natalie Landa, Firas Younis, Kenneth Hollander, Eric Mayoux, Lea Rath-Wolfson, Talma Rosenthal
OBJECTIVE: Hypertension and Diabetes commonly coexist and have been implicated in deterioration of kidneys, heart and impairment of pancreas. Empagliflozin (Empa), a selective SGLT2 inhibitor, is a new agent for treatment of diabetes via enhancing glucosuria, independent of insulin resistance. This study evaluates Empa's prophylactic beneficial effect on glomerular, cardiac and pancreatic integrity, in CRDH animals. DESIGN AND METHOD: Cohen Rosenthal Diabetic Hypertensive rats (CRDH) were divided into 3 groups: A- Sugar diet (SD) + Empa, B-Sugar Diet + Veh, C-Regular Chow + Veh (Control)...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27752710/empagliflozin-decreases-myocardial-cytoplasmic-na-through-inhibition-of-the-cardiac-na-h-exchanger-in-rats-and-rabbits
#19
Antonius Baartscheer, Cees A Schumacher, Rob C I Wüst, Jan W T Fiolet, Ger J M Stienen, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Empagliflozin (EMPA), an inhibitor of the renal sodium-glucose cotransporter (SGLT) 2, reduces the risk of cardiovascular death in patients with type 2 diabetes. The underlying mechanism of this effect is unknown. Elevated cardiac cytoplasmic Na(+) ([Na(+)]c) and Ca(2+) ([Ca(2+)]c) concentrations and decreased mitochondrial Ca(2+) concentration ([Ca(2+)]m) are drivers of heart failure and cardiac death. We therefore hypothesised that EMPA would directly modify [Na(+)]c, [Ca(2+)]c and [Ca(2+)]m in cardiomyocytes...
October 17, 2016: Diabetologia
https://www.readbyqxmd.com/read/27744129/effects-of-reducing-blood-pressure-on-cardiovascular-outcomes-and-mortality-in-patients-with-type-2-diabetes-focus-on-sglt2-inhibitors-and-empa-reg-outcome
#20
André J Scheen
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has shown a remarkable reduction in cardiovascular and all-cause mortality in patients with type 2 diabetes (T2D) and antecedents of cardiovascular disease in the EMPA-REG OUTCOME trial. This effect has been attributed to a hemodynamic rather than a metabolic effect, partly due to the osmotic/diuretic effect of empagliflozin and to the reduction in arterial blood pressure. The present review will: (1) summarize the results of specific studies having tested the blood pressure lowering effects of SGLT2 inhibitors; (2) describe the results of meta-analyses of trials having evaluated the effects on mortality and cardiovascular outcomes of lowering blood pressure in patients with T2D, with a special focus on baseline and target blood pressures; (3) compare the cardiovascular outcome results in EMPA-REG OUTCOME versus other major trials with antihypertensive agents in patients with T2D; and (4) evaluate post-hoc analyses from EMPA-REG OUTCOME, especially subgroups of patients of special interest regarding the blood pressure lowering hypothesis...
September 28, 2016: Diabetes Research and Clinical Practice
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