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Empagliflozine

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https://www.readbyqxmd.com/read/28325783/renal-handling-of-ketones-in-response-to-sodium-glucose-cotransporter-2-inhibition-in-patients-with-type-2-diabetes
#1
Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
OBJECTIVE: Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS: We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min(-1) · 1...
March 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28324484/sodium-glucose-co-transporter-2-sglt2-inhibitor-comparing-trial-data-and-real-world-use
#2
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/28323967/all-cause-mortality-in-patients-with-diabetes-under-treatment-with-dapagliflozin-a-population-based-open-cohort-study-in-thin-database
#3
Konstantinos A Toulis, Brian H Willis, Tom Marshall, Balachadran Kumarendran, Krishna Gokhale, Sandip Ghosh, G Neil Thomas, Kar Keung Cheng, Parth Narendran, Wasim Hanif, Krishnarajah Nirantharakumar
Context: Empagliflozin was found to decrease mortality in patients with type 2 diabetes (T2DM) and a prior cardiovascular (CVD) event. Objectives: To establish whether these benefits can be replicated in a real-world setting, should be expected with the use of dapagliflozin, and apply to T2DM patients at low risk of CVD. Design: General Practice, population-based, retrospective cohort study (January 2013-September 2015). Setting: The Health Improvement Network Database (THIN)...
February 20, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#4
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFA) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323512/evaluating-the-costs-of-glycemic-response-with-canagliflozin-versus-dapagliflozin-and-empagliflozin-as-add-on-to-metformin-in-patients-with-type-2-diabetes-mellitus-in-the-united-arab-emirates
#5
Agata Schubert, Anders T Buchholt, Antoine C El Khoury, Ahmed Kamal, Vanessa Taieb
OBJECTIVE: This study evaluates the cost of achieving glycemic control with 3 sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE). METHODS: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014...
March 21, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28322073/sglt2-inhibitor-dpp-4-inhibitor-combination-therapy-complementary-mechanisms-of-action-for-management-of-type-2-diabetes-mellitus
#6
Jayant Dey
Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence...
March 21, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28300428/empa-s-new-clothes-the-untold-story-of-the-empa-reg-outcome-trial
#7
Aus Alzaid
It is no secret that the diabetes community has been yearning for good news for quite some time. One outstanding issue undermining effective diabetes management has been the lack of demonstrable effects of glycemic interventions on cardiovascular (CV) outcome in people with type 2 diabetes. This, however, seems to have changed recently after the publication of the Empa-Reg Outcome Trial. The study reported an impressive reduction in CV deaths that was observed within weeks of treatment with the diabetes agent, Empagliflozin...
March 16, 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#8
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
#9
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/28290274/relative-bioavailability-of-an-empagliflozin-25-mg-linagliptin-5-mg-fixed-dose-combination-tablet%C3%A2
#10
Stephan Glund, Michaela Mattheus, Frank Runge, Peter Rose, Christian Friedrich
OBJECTIVE: This relative bioavailability study compared a fixed-dose combination (FDC) tablet of empagliflozin 25 mg/linagliptin 5 mg with the corresponding individual components. In addition, the effect of food on the bioavailability of the FDC was studied, and the standard-dissolving formulation FDC was compared with a slow-dissolving side batch. METHODS: An open-label, randomized, crossover study design was used (ClinicalTrials.gov Identifier NCT01189201). Healthy volunteers (n = 42) each received three single-dose treatments: FDC standard dissolution, individual tablets, and either FDC standard dissolution with food or FDC slow dissolution...
March 14, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28264617/integrated-cardiovascular-safety-multifaceted-considerations-in-drug-development-and-therapeutic-use
#11
J Rick Turner
Cardiovascular safety has become a central component of contemporary drug development and therapeutic use since noncardiovascular drugs can exert cardiovascular harms. Appropriate preapproval investigations and monitoring during clinical practice are therefore advantageous. Areas covered: Integrated cardiovascular safety is a broad field of investigation. This review focuses on three areas of assessment specifically chosen to exemplify advances and challenges in this field: the cardiotoxicity of oncologic agents, off-target blood pressure (BP) increases to noncardiovascular drugs, and the cardiovascular safety of new antidiabetic drugs for type 2 diabetes (T2D)...
March 6, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28254770/sglt2-inhibition-in-the-diabetic-kidney-from-mechanisms-to-clinical-outcome
#12
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/28240446/sodium-glucose-cotransporter-2-inhibitors-and-risk-of-adverse-renal-outcomes-among-type-2-diabetes-patients-a-network-and-cumulative-meta-analysis-of-randomized-controlled-trials
#13
Huilin Tang, Dandan Li, Jingjing Zhang, Yufeng Li, Tiansheng Wang, Suodi Zhai, Yiqing Song
AIM: The renal safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) remains uncertain. This meta-analysis aimed to compare the effects of each SGLT2 inhibitor on adverse renal outcomes in patients with T2DM. METHODS: PubMed, EMBASE, CENTRAL, and ClinicalTrials.gov were searched up to May 24 2016 without language or date restrictions. Randomized trials that reporting at least one renal-related adverse outcome in T2DM patients treated with SGLT2 inhibitors were included...
February 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28217527/vascular-legacy-hope-advances-to-empa-reg-and-leader-a-surprising-similarity
#14
Sanjay Kalra, Rakesh Sahay
Recently reported cardiovascular outcome studies on empagliflozin (EMPA-REG) and liraglutide (LEADER) have spurred interest in this field of diabetology. This commentary compares and contrasts these studies with two equally important outcome trials conducted using blood pressure lowering agents. A comparison with MICROHOPE (using ramipril) and ADVANCE (using perindopril + indapamide) blood pressure arms throws up interesting facts. The degree of blood pressure lowering, dissociation between cardiovascular and cerebrovascular benefits, and discordance between renal and retinal outcomes are surprisingly similar in these trials, conducted using disparate molecules...
January 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28203358/the-renal-effects-of-sglt2-inhibitors-and-a-mini-review-of-the-literature
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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