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https://www.readbyqxmd.com/read/28203358/the-renal-effects-of-sglt2-inhibitors-and-a-mini-review-of-the-literature
#1
REVIEW
Vasileios Andrianesis, Spyridoula Glykofridi, John Doupis
Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM)...
December 2016: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28197977/interpreting-cardiovascular-endpoints-in-trials-of-antihyperglycemic-drugs
#2
REVIEW
Himika Chawla, Nikhil Tandon
In view of the significant cardiovascular (CV) morbidity and mortality in patients with type 2 diabetes mellitus, and concerns raised about the CV safety of some glucose-lowering drugs, the US Food and Drug Administration (FDA) issued guidance for the industry in 2008 to demonstrate CV safety for the approval of all new antihyperglycemic drugs. Seven randomized controlled trials involving around 60,000 participants have been completed so far and have demonstrated the CV safety of dipeptidyl peptidase 4 inhibitors (saxagliptin, alogliptin and sitagliptin), glucagon-like peptide-1 receptor agonists (lixisenatide, liraglutide and semaglutide) and a sodium-glucose co-transporter 2 inhibitor (empagliflozin) in patients with type 2 diabetes...
February 14, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
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
#3
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
#4
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
#5
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
#6
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
#7
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/28151516/-cardiovascular-disease-in-diabetic-patients-risk-factors-clinical-history-and-prevention
#8
Angelo Avogaro
Cardiovascular disease (CVD) is the leading cause of death in patients with diabetes mellitus (DM) in which there is a rapid evolution and widespread early atherosclerosis, whose causes are manifold. In the presence of hyperglycemia there is the activation of multiple signaling responses involving, first endothelial activation and later dysfunction, which are the first detectable step toward the atherosclerotic disease. A healthy lifestyle is the cornerstone for the prevention and control of CVD in patients with DM, in whom we must pursue the control, not only of blood sugar levels, but also of all risk factors for CVD...
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
#9
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
#10
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
#11
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/28134748/influence-of-common-polymorphisms-in-the-slc5a2-gene-on-metabolic-traits-in-subjects-at-increased-risk-of-diabetes-and-on-response-to-empagliflozin-treatment-in-patients-with-diabetes
#12
Heike Zimdahl, Axel Haupt, Michael Brendel, Louis Bour, Fausto Machicao, Afshin Salsali, Uli C Broedl, Hans-Juergen Woerle, Hans-Ulrich Häring, Harald Staiger
OBJECTIVE: Inhibition of the renal sodium-glucose cotransporter 2 (SGLT2) is a novel concept in the therapy of diabetes mellitus. In this study, we first assessed whether common single nucleotide polymorphisms (SNPs) in the SGLT2-encoding gene SLC5A2 affect diabetes-related metabolic traits in subjects at risk for type 2 diabetes and, second, whether these have pharmacogenetic relevance by interfering with the response to empagliflozin treatment in patients with type 2 diabetes. PATIENTS AND METHODS: Samples from a metabolically well-phenotyped cross-sectional study population (total N=2600) at increased risk for type 2 diabetes and pooled pharmacogenetic samples from patients from four phase III trials of empagliflozin (in total: 603 receiving empagliflozin, 305 receiving placebo) were genotyped for five common SNPs (minor allele frequencies ≥5%) present in the SLC5A2 gene locus...
January 27, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28131656/integration-of-recent-evidence-into-management-of-patients-with-atherosclerotic-cardiovascular-disease-and-type-2-diabetes
#13
REVIEW
Eberhard Standl, Oliver Schnell, Darren K McGuire, Antonio Ceriello, Lars Rydén
Cardiovascular outcome trials of antihyperglycaemic drugs and non-statin LDL-cholesterol-lowering drugs in patients with type 2 diabetes who have, or who are at high risk of, atherosclerotic cardiovascular disease have provided new evidence that has substantially affected the management of cardiovascular risk in these patients. On the basis of proven cardiovascular and renal benefit, the antihyperglycaemic drugs empagliflozin, liraglutide, and semaglutide-the latter being under review for approval by the US Food and Drug Administration and the European Medicines Agency-should be preferentially used as second-line treatments in these patient populations, typically in addition to metformin...
January 25, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28128510/determinants-of-the-increase-in-fasting-plasma-ketone-concentration-during-sglt2-inhibition-in-ngt-ifg-and-t2dm-patients
#14
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
AIM: To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration RESEARCH DESIGN AND METHODS: Fasting plasma glucose, insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at 1 and 14 days after treatment with empagliflozin. RESULTS: Empagliflozin caused 38 mg/dl reduction in the fasting plasma glucose (FPG) concentration in T2DM patients...
January 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28121469/savor-timi-to-sustain-6-a-critical-comparison-of-cardiovascular-outcome-trials-of-antidiabetic-drugs
#15
Awadhesh Kumar Singh, Ritu Singh
Since the inception of mandatory cardiovascular (CV) safety outcome trial (CVOT) promulgated by US FDA in 2008, seven trials have so far been published with three different classes of antidiabetic drugs in type 2 diabetes mellitus (T2DM). This mini-review aims to critically analyse these CVOTs in terms of different outcomes achieved. Areas covered: An electronic search pertaining to the subject was conducted till September 2016. The three CVOT conducted with saxagliptin, alogliptin and sitagliptin respectively, found them to be CV-neutral...
February 6, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28120716/sglt-2-inhibitors-and-cardiovascular-risk-in-diabetes-mellitus-a-comprehensive-and-critical-review-of-the-literature
#16
Konstantinos Imprialos, Charles Faselis, Chrysoula Boutari, Konstantinos Stavropoulos, Vasilios Athyros, Asterios Karagiannis, Michael Doumas
BACKGROUND: Diabetes mellitus is a major cardiovascular risk factor. Despite the vast pharmaceutical armamentarium, current therapeutic options for the treatment of type 2 diabetes mellitus were unable to provide consistent cardiovascular benefits, apart for metformin. The newest antidiabetic class of drugs, the SGLT-2 inhibitors, seem to provide significant survival benefits. The aim of this review is to present available data that will clarify whether SGLT-2 inhibitors could precipitate in reducing cardiovascular risk in diabetes mellitus...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28120022/-cardiovascular-aspects-of-diabetes-treatment-finally-a-reason-for-cardiologists-to-be-pleased
#17
T Forst, L Plum-Mörschel, M M Weber
Cardiovascular disease significantly determines morbidity and mortality in patients with diabetes mellitus type 2. Large clinical trials in the past left controversial evidence about the effect of blood glucose-lowering treatments on cardiovascular outcomes. In 2008, the regulatory authorities defined new requirements on cardiovascular safety data for the approval of new drugs for the treatment of type 2 diabetes mellitus. Since then, numerous large safety studies have been initiated to prove cardiovascular noninferiority of new antidiabetic drugs...
January 24, 2017: Der Internist
https://www.readbyqxmd.com/read/28109083/green-pharmaceutical-analysis-of-drugs-coformulated-with-highly-different-concentrations-using-spiking-and-manipulation-of-their-ratio-spectra
#18
Bassam M Ayoub
Introducing green analysis to pharmaceuticalproducts is considered a significant approach topreserving the environment. This method can be anenvironmentally friendly alternative to the existingmethods, accompanied by a validated automatedprocedure for the analysis of a drug with the lowestpossible number of samples. Different simplespectrophotometric methods were developed forthe simultaneous determination of empagliflozin(EG) and metformin (MT) by manipulating their ratiospectra in their application on a recently approvedpharmaceutical combination, Synjardy tablets...
January 20, 2017: Journal of AOAC International
https://www.readbyqxmd.com/read/28106149/blood-pressure-reduction-in-diabetes-lessons-from-accord-sprint-and-empa-reg-outcome
#19
REVIEW
Pantelis A Sarafidis, Antonios A Lazaridis, Gema Ruiz-Hurtado, Luis M Ruilope
In patients with diabetes mellitus, the presence of hypertension substantially increases the risk of cardiovascular events, and reductions in blood pressure (BP) can reduce cardiovascular morbidity and mortality. Following evidence from trials randomizing patients to diastolic BP levels, previous guidelines recommended an office BP target of <130/80 mmHg in individuals with diabetes mellitus. However, the evidence for this systolic BP (SBP) target was derived from observational studies. When the results of the ACCORD-BP study showed that those individuals with diabetes mellitus and a target BP of <120 mmHg had a cardiovascular risk that is similar to those with <140 mmHg, all guidelines returned to a recommended SBP of <140 mmHg...
January 20, 2017: Nature Reviews. Endocrinology
https://www.readbyqxmd.com/read/28105986/canagliflozin-dapagliflozin-and-empagliflozin-monotherapy-for-treating-type-2-diabetes-systematic-review-and-economic-evaluation
#20
Rhona Johnston, Olalekan Uthman, Ewen Cummins, Christine Clar, Pamela Royle, Jill Colquitt, Bee Kang Tan, Andrew Clegg, Saran Shantikumar, Rachel Court, J Paul O'Hare, David McGrane, Tim Holt, Norman Waugh
BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors...
January 2017: Health Technology Assessment: HTA
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