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https://www.readbyqxmd.com/read/28324484/sodium-glucose-co-transporter-2-sglt2-inhibitor-comparing-trial-data-and-real-world-use
#1
Andrew McGovern, Michael Feher, Neil Munro, Simon de Lusignan
INTRODUCTION: The first cardiovascular safety trial in the sodium-glucose co-transporter-2 (SGLT2) inhibitor drug class, the Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, demonstrated significant cardiovascular risk reduction with empagliflozin. It is currently not clear what proportions of people with type 2 diabetes (T2DM) have the same high cardiovascular risk as those included in the trial, and will therefore be likely to experience the same cardiovascular benefit...
March 21, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28324025/clinical-and-genetic-features-of-patients-with-type-2-diabetes-and-renal-glycosuria
#2
Siqian Gong, Jiandong Guo, Xueyao Han, Meng Li, Lingli Zhou, Xiaoling Cai, Yu Zhu, Yingying Luo, Simin Zhang, Xianghai Zhou, Yumin Ma, Linong Ji
Context: A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was recently reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. Mutations in SLC5A2 and HNF1A are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood. Objective: To assess the clinical features of T2DM patients with renal glycosuria and those with low urinary glucose excretion (LUGE) and identify variants in the coding regions of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM...
January 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#3
REVIEW
Pieter Martens, Chantal Mathieu, Frederik H Verbrugge
This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#4
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
January 28, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28277831/dapagliflozin-potential-beneficial-effects-in-the-prevention-and-treatment-of-renal-and-cardiovascular-complications-in-patients-with-type-2-diabetes
#5
Paola Fioretto, Angelo Avogaro
Diabetic kidney disease is the leading cause of end-stage renal disease, a significant contributor to cardiovascular (CV) disease, responsible for much of the morbidity and mortality in patients with type 2 diabetes (T2DM). Strategies to slow or prevent the onset and progression of diabetic kidney disease are critical for effectively managing T2DM and reducing CV risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic agents, which may provide nephroprotective and CV protective effects...
March 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28262472/the-role-of-sodium-glucose-cotransporter-2-inhibitors-in-the-management-of-type-2-diabetes
#6
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...
March 3, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28255241/an-evidence-based-practice-oriented-review-focusing-on-canagliflozin-in-the-management-of-type-2-diabetes
#7
REVIEW
Joseph A Messana, Stanley S Schwartz, Raymond R Townsend
Caring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia. The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the sodium-glucose-linked transporter type 2 (SGLT2) inhibitors, which work principally in the proximal tubule of the kidney to block filtered glucose reabsorption. In the few years attending this new class arrival in the market, there has been a great deal of interest generated by the novel mechanism of action of SGLT2 inhibitors and by recent large outcome trials suggesting benefit on important clinical outcomes such as death, cardiovascular disease and kidney disease progression...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28254770/sglt2-inhibition-in-the-diabetic-kidney-from-mechanisms-to-clinical-outcome
#8
Erik J M van Bommel, Marcel H A Muskiet, Lennart Tonneijck, Mark H H Kramer, Max Nieuwdorp, Daniel H van Raalte
Diabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously...
March 2, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28253918/luseogliflozin-reduces-epicardial-fat-accumulation-in-patients-with-type-2-diabetes-a-pilot-study
#9
Ryotaro Bouchi, Masahiro Terashima, Yuriko Sasahara, Masahiro Asakawa, Tatsuya Fukuda, Takato Takeuchi, Yujiro Nakano, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
BACKGROUND: Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV...
March 3, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28251513/intensifying-treatment-beyond-monotherapy-in-type-2-diabetes-mellitus-where-do-newer-therapies-fit
#10
REVIEW
Alexander Kuhn, Jean Park, Adline Ghazi, Vanita R Aroda
PURPOSE OF REVIEW: Guidelines for a standard second diabetes medication for the treatment of type 2 diabetes (T2DM) have yet to be established. The rapid increase in the number of newer therapies available makes the choice more difficult. Thus, we reviewed clinical trial evidence evaluating newer therapies available for treatment intensification beyond monotherapy. RECENT FINDINGS: Head-to-head studies comparing newer therapies versus traditional (i.e., sulfonylurea) approaches consistently find lower incidence of hypoglycemia and weight gain with newer therapies...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28241822/effects-of-canagliflozin-a-sodium-glucose-co-transporter-2-inhibitor-on-blood-pressure-and-markers-of-arterial-stiffness-in-patients-with-type-2-diabetes-mellitus-a-post-hoc-analysis
#11
Michael Pfeifer, Raymond R Townsend, Michael J Davies, Ujjwala Vijapurkar, Jimmy Ren
BACKGROUND: Physiologic determinants, such as pulse pressure [difference between systolic blood pressure (SBP) and diastolic BP (DBP)], mean arterial pressure (2/3 DBP + 1/3 SBP), and double product [beats per minute (bpm) × SBP], are linked to cardiovascular outcomes. The effects of canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, on pulse pressure, mean arterial pressure, and double product were assessed in patients with type 2 diabetes mellitus (T2DM). METHODS: This post hoc analysis was based on pooled data from four 26-week, randomized, double-blind, placebo-controlled studies evaluating canagliflozin in patients with T2DM (N = 2313) and a 6-week, randomized, double-blind, placebo-controlled, ambulatory BP monitoring (ABPM) study evaluating canagliflozin in patients with T2DM and hypertension (N = 169)...
February 27, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28178390/metabolic-and-hemodynamic-effects-of-sodium-dependent-glucose-co-transporter-2-inhibitors-on-cardio-renal-protection-in-the-treatment-of-patients-with-type-2-diabetes-mellitus
#12
REVIEW
Atsunori Kashiwagi, Hiroshi Maegawa
The specific Na+/glucose co-transporter 2 inhibitors (SGLT2 inhibitors) inhibit glucose reabsorption in proximal renal tubular cells, and both fasting and postprandial glucose significantly decrease due to urinary glucose loss. As a result, pancreatic β-cell function and peripheral insulin action significantly improve with relief from glucose toxicity. Furthermore, whole body energy metabolism changes to relative glucose deficiency and triggers increased lipolysis in fat cells, and fatty acid oxidation and then ketone body production in the liver during treatment with SGLT2 inhibitors...
February 8, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28159856/sglt2-inhibitor-empagliflozin-reduces-renal-outcomes-and-dampens-the-progressive-reduction-in-glomerular-filtration-rate-in-patients-with-type-2-diabetes-and-antecedents-of-cardiovascular-disease
#13
https://www.readbyqxmd.com/read/28153377/effects-of-reducing-blood-pressure-on-renal-outcomes-in-patients-with-type-2-diabetes-focus-on-sglt2-inhibitors-and-empa-reg-outcome
#14
REVIEW
A J Scheen, P Delanaye
Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, has enabled remarkable reductions in cardiovascular and all-cause mortality as well as in renal outcomes in patients with type 2 diabetes (T2D) and a history of cardiovascular disease in the EMPA-REG OUTCOME. These results have been attributed to haemodynamic rather than metabolic effects, in part due to the osmotic/diuretic action of empagliflozin and the reduction in arterial blood pressure (BP). The present narrative review includes the results of meta-analyses of trials evaluating the effects on renal outcomes of lowering BP in patients with T2D, with a special focus on the influence of baseline and achieved systolic BP, and compares the renal outcome results of the EMPA-REG OUTCOME with those of other major trials with inhibitors of the renin-angiotensin system in patients with T2D and the preliminary findings with other SGLT2 inhibitors, and also evaluates post hoc analyses from the EMPA-REG OUTCOME of special interest as regards the BP-lowering hypothesis and renal function...
January 30, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28151518/-type-2-diabetes-treatment-and-cardiovascular-risk-what-can-we-learn-from-trials
#15
Agostino Consoli, Fabrizio Febo
Diabetes treatment should include drugs with absolutely no adverse effects toward cardiovascular risk. Indeed, it would be advisable to use drugs with intrinsic protective effect against the risk of cardiovascular events. Intervention trials aiming at demonstrating a protective cardiovascular effect of very tight glucose control have produced controversial results. It is commonly perceived, however, that early intervention with safe treatment strategies is likely to be beneficial. In regard to safety, in the attempt to firmly establish cardiovascular safety of new drugs for diabetes, Government Authorities have mandated that cardiovascular safety trials need to be performed for all new drugs registered for diabetes treatment...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28151517/-effects-of-glucagon-like-peptide-1-receptor-agonists-on-cardiovascular-risk-factors-and-the-cardiovascular-system
#16
Teresa Vanessa Fiorentino, Giorgio Sesti
The results of the cardiovascular outcome trials comparing the SGLT2 inhibitor empagliflozin and the glucagon-like peptide-1 receptor agonist liraglutide to placebo have been recently published. Interestingly, empagliflozin and liraglutide treatments significantly reduce cardiovascular events in subjects with type 2 diabetes. The mechanisms underlying the observed cardioprotective effects of empagliflozin and liraglutide are speculative and future studies are needed to better understand these results. However, since reduction in the primary outcome was evident 3 months after starting empagliflozin and 24 months after starting liraglutide, it is tempting to hypothesize that the cardiovascular benefits observed in diabetic patients treated with empagliflozin are due to its hemodynamic effects and to metabolic substrate shift induced by the mild and persistent hyperketonemia, while the positive effects of liraglutide treatment may be attributable to biologic changes of atherosclerotic lesions...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28144158/following-the-results-of-the-empa-reg-outcome-trial-with-empagliflozin-is-it-possible-to-speak-of-a-class-effect
#17
Francisco Javier Ampudia-Blasco, Irene Romera, Bernat Ariño, Ramón Gomis
BACKGROUND: The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/28144148/advances-in-the-management-of-cardiovascular-risk-for-patients-with-type-2-diabetes-perspectives-from-the-academy-for-cardiovascular-risk-outcomes-and-safety-studies-in-type-2-diabetes
#18
Guntram Schernthaner, Sarah Jarvis, Chaim Lotan, Martin Prázný, Christoph Wanner, Thomas C Wascher
Diabetes is a global health emergency projected to affect 642 million people by 2040. Type 2 diabetes (T2D) represents 90% of diabetes cases and is associated with a range of cardiovascular (CV) risk factors that are more than double the incidence of CV disease and significantly increase mortality rates. Diabetes treatments have typically focused on improving glycemic control but their effect on CV outcomes has remained uncertain. In 2008, the US Food and Drug Administration (FDA) looked to address this knowledge gap and mandated CV outcome trials (CVOTs) for all new antidiabetic therapies...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28138853/sodium-glucose-co-transporter-2-sglt2-inhibitors-comparing-trial-and-real-world-use-study-protocol
#19
Andrew McGovern, Michael Feher, Neil Munro, Simon de Lusignan
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors (gliflozins) are the newest class of medication available to treat type 2 diabetes (T2DM). Recent findings from the first complete cardiovascular safety trial in SGLT2 inhibitors, the Empagliflozin, Cardiovascular Outcomes, and Mortality in type 2 diabetes (EMPA-REG OUTCOMES) trial, demonstrated reduced cardiovascular outcomes in people with high cardiovascular risk. How to apply these findings to clinical practice remains unclear, with questions remaining on who will reap this cardiovascular benefit...
January 30, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28120497/rationale-design-and-baseline-characteristics-of-the-canagliflozin-cardiovascular-assessment-study-renal-canvas-r-a-randomized-placebo-controlled-trial
#20
Bruce Neal, Vlado Perkovic, David R Matthews, Kenneth W Mahaffey, Greg Fulcher, Gary Meininger, Ngozi Erondu, Mehul Desai, Wayne Shaw, Frank Vercruysse, Jacqueline Yee, Hsiaowei Deng, Dick de Zeeuw
AIMS: The primary aim of the CANagliflozin cardioVascular Assessment Study-Renal (CANVAS-R) is to determine whether the favourable effects of inhibition of the sodium glucose co-transporter 2 (SGLT2) on blood glucose, blood pressure and body weight are accompanied by protection against adverse renal outcomes. MATERIALS AND METHODS: CANVAS-R is a prospective, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes with a history or high risk of cardiovascular events...
March 2017: Diabetes, Obesity & Metabolism
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