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Empagliflozine

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https://www.readbyqxmd.com/read/29445145/canagliflozin-mediated-dual-inhibition-of-mitochondrial-glutamate-dehydrogenase-and-complex-i-an-off-target-adverse-effect
#1
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29430814/sglt-2-inhibitors-and-the-risk-of-lower-limb-amputation-is-this-a-class-effect
#2
Charles Khouri, Jean-Luc Cracowski, Matthieu Roustit
OBJECTIVE: Inhibitors of the sodium-glucose co-transporter-2 (SGLT-2) are a novel class of glucose lowering agents showing promising results. However, the use of canagliflozin has been associated with an increased risk of lower-limb amputation. Whether this risk concerns other SGLT-2 inhibitors is unclear. METHODS: We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase®) to address this issue. RESULTS: Among the 8,293,886 reports available between January 2013 and December 2017, we identified 79 reports of lower-limb amputations associated with SGLT-2 inhibitors...
February 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29412698/the-organic-anion-transporter-oat3-enhances-the-glucosuric-effect-of-the-sglt2-inhibitor-empagliflozin
#3
Yiling Fu, Davorka Breljak, Akira Onishi, Falk Batz, Rohit Patel, Winnie Huang, Panai Song, Brent Freeman, Eric Mayoux, Hermann Koepsell, Naohiko Anzai, Sanjay K Nigam, Ivan Sabolić, Volker Vallon
The SGLT2 inhibitor empagliflozin (plasma protein binding ~88%) may reach its target in the brush border of the early proximal tubule by glomerular filtration and tubular secretion. Here we determined whether empagliflozin is secreted by renal tubules, and whether genetic knockout of the basolateral organic anion transporter Oat3 (-/-) affects its tubular secretion or glucosuric effect. Renal clearance studies in wild-type (WT) mice showed that tubular secretion accounted for 50-70% of empagliflozin urinary excretion...
February 7, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29412119/sodium-glucose-cotransporter-2-inhibitors-and-ischemic-stroke
#4
Dimitrios Milonas, Konstantinos Tziomalos
BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with substantially increased risk for cardiovascular events, including ischemic stroke. In turn, ischemic stroke represents a leading cause of mortality and long-term disability worldwide. The newest class of glucose-lowering agents is sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which act through inhibition of glucose reabsorption in the kidney, resulting in glucose excretion without stimulating insulin release. Accumulating data suggests that these agents improve multiple risk factors for ischemic stroke except their glucose-lowering effect...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29409087/-chronic-kidney-disease-update-2018
#5
Markus Ketteler, Christoph Wanner
SGLT2-INHIBITION IN DIABETIC AND NON-DIABETIC KIDNEY DISEASE:  The CANVAS Program Collaborative Group study confirmed nephroprotective actions by canagliflocin comparable to empagliflozin as published in the EMPA-REG Outcome study. Treatment with Liraglutide (LEADER study) also suggests nephroprotection via albuminuria reduction a decreased eGFR decline in subgroups and depending on stages of diabetic nephropathy. KDIGO CKD-MBD GUIDELINE UPDATE 2017:  In July 2017, an update of the KDIGO (Kidney Disease: Improving Global Outcomes) 2009 guideline on diagnostic and treatment chronic kidney disease - mineral and bone disorders (CKD-MBD) was published...
February 2018: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/29388411/-sglt2-inhibitor-or-glp-1-receptor-agonist-in-a-patient-with-type-2-diabetes-and-cardiovascular-disease
#6
A J Scheen, N Paquot
Two classes of antidiabetic agents have shown a cardiovascular and renal protection in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, and liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, were granted a reduction of major cardiovascular events and mortality after the positive results of EMPA-REG OUTCOME and LEADER outcome trials, respectively. Protection mechanisms most probably differ between the two pharmacological classes and are perhaps complementary...
January 2018: Revue Médicale de Liège
https://www.readbyqxmd.com/read/29376471/emerging-roles-of-sglt2-inhibitors-in-obesity-and-insulin-resistance-focus-on-fat-browning-and-macrophage-polarization
#7
Liang Xu, Tsuguhito Ota
Obesity-associated low-grade inflammation underlies insulin resistance and associated metabolic comorbidities, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease. Excessive ectopic fat deposition in obesity causes disorders of energy homeostasis and low-grade chronic inflammation in metabolic tissues. In particular, obesity-induced recruitment and activation of adipose tissue macrophages play a key role in the pathogenesis of insulin resistance and T2D. Therefore, treatment options for energy metabolism and macrophage polarization in obese subjects are needed...
December 11, 2017: Adipocyte
https://www.readbyqxmd.com/read/29372664/sodium-glucose-co-transporter-2-inhibitors-and-cardiovascular-outcomes-a-systematic-review-and-meta-analysis
#8
Muhammad Shariq Usman, Tariq Jamal Siddiqi, Muhammad Mustafa Memon, Muhammad Shahzeb Khan, Wasiq Faraz Rawasia, Muhammad Talha Ayub, Jayakumar Sreenivasan, Yasmeen Golzar
Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29368701/effect-of-glucose-lowering-therapies-on-heart-failure
#9
REVIEW
Michael Nassif, Mikhail Kosiborod
Heart failure is one of the most common comorbidities of diabetes mellitus. Glucose-lowering therapies that can prevent heart failure or improve outcomes in patients with established heart failure are of critical importance among those with type 2 diabetes. Several types of glucose-lowering drugs have been assessed in this setting. Metformin has been shown to modestly improve the outcomes of patients with heart failure, whereas the effect of insulin in those with established heart failure is less clear. The effect of sulfonylureas on improving heart failure is controversial; observational reports have suggested that they are harmful in these patients, but these data have not been confirmed in randomized, controlled trials...
January 25, 2018: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29359260/clinical-impact-of-oral-antidiabetic-medications-in-heart-failure-patients
#10
REVIEW
Alberto Palazzuoli, Elena Ceccarelli, Gaetano Ruocco, Ranuccio Nuti
Heart failure (HF) is a common complication in patients with type 2 diabetes and it is closely associated with high morbidity and mortality rate. The incidence of cardiovascular events in patients with diabetes is related to high levels of glycemia, expressed by increase of HbA1c levels. However, there is little evidence to indicate that glycemic control can reduce the incidence of HF events in this population. Recently, several new antidiabetic drugs have been proposed although the exact clinical impact on heart failure occurrence and deterioration is under debate...
January 23, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29358464/mortality-reduction-in-empa-reg-outcome-trial-beyond-the-antidiabetes-effect
#11
Samy Suissa
Two recent large-scale cardiovascular outcome trials, a now common tool in assessing the safety of pharmacological treatments for type 2 diabetes, reported significant reductions in all-cause mortality. In EMPA-REG OUTCOME [BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients], patients who received the SGLT2 inhibitor empagliflozin had a notable reduction of 9.2 deaths per 1,000 per year, while LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation) found that the patients receiving the GLP-1 receptor agonist liraglutide had a reduction of 3...
February 2018: Diabetes Care
https://www.readbyqxmd.com/read/29349708/cost-effectiveness-of-empagliflozin-for-the-treatment-of-patients-with-type-2-diabetes-mellitus-at-increased-cardiovascular-risk-in-greece
#12
George Gourzoulidis, Charalampos Tzanetakos, Ioannis Ioannidis, Apostolos Tsapas, Georgia Kourlaba, Giannis Papageorgiou, Nikos Maniadakis
BACKGROUND AND OBJECTIVE: Type 2 diabetes mellitus (T2DM) is frequently associated with co-morbidities that exacerbate cardiovascular (CV) risk. CV disease is the leading cause of death in people with diabetes across the world and accounts for approximately half the deaths in the T2DM population. Hence, the objective of present study was to evaluate the cost-effectiveness of empagliflozin, in addition to standard of care (SoC), for the treatment of adult patients with T2DM and high CV risk in Greece...
January 18, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29349558/sglt2-inhibitors-and-mechanisms-of-hypertension
#13
REVIEW
Alexandros Briasoulis, Omar Al Dhaybi, George L Bakris
PURPOSE OF REVIEW: We sought to review currently available data on the safety and efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in type 2 diabetes mellitus patients with hypertension. RECENT FINDINGS: Inhibition of SGLT2 in the renal proximal tubule results in increased urinary glucose excretion and modest improvements of hemoglobin A1C. Treatment with any of the three currently FDA-approved SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) results in sustained systolic and diastolic blood pressure reduction, in part via minimal natriuresis and possible reductions in sympathetic tone...
January 19, 2018: Current Cardiology Reports
https://www.readbyqxmd.com/read/29342295/empagliflozin-treatment-is-associated-with-improved-beta-cell-function-in-t2dm
#14
Hussein Al Jobori, Giuseppe Daniele, John Adams, Eugenio Cersosimo, Carolina Solis-Herrera, Curtis Triplitt, Ralph A DeFronzo, Muhammad Abdul-Ghani
Objective: To examine whether lowering the plasma glucose concentration with empagliflozin (SGLT2 inhibitor) improves beta cell function in T2DM. Research Design and Methods: 15 T2DM patients received empagliflozin (25 mg/day) for 2 weeks, and beta cell function was measured with 9-step hyperglycemic clamp (each step = +40 mg/dl) before and 48 hours and 14 days after empagliflozin. Results: Empagliflozin caused 101±10 and 117±11 grams glucosuria on days 1 and 14 and produced 25±6 and 38±8 mg/dl reduction (p<0...
January 12, 2018: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#15
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29322486/dapagliflozin-and-empagliflozin-ameliorate-hepatic-dysfunction-among-chinese-subjects-with-diabetes-in-part-through-glycemic-improvement-a-single-center-retrospective-observational-study
#16
Paul Chi Ho Lee, Yunjuan Gu, Man Yi Yeung, Carol Ho Yi Fong, Yu Cho Woo, Wing Sun Chow, Kathryn Tan, Karen Siu Ling Lam
INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic dysfunction, although studies focusing on their underlying mechanisms are lacking, especially ones on dapagliflozin and empagliflozin. Here, we investigated the relationship between amelioration of hepatic dysfunction and improvement in various metabolic parameters among Chinese subjects with type 2 diabetes (T2DM). METHODS: This was a single-center, retrospective, observational study that involved 115 Chinese participants with T2DM treated with either dapagliflozin or empagliflozin for at least 6 months between July 2016 and February 2017...
January 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29322280/direct-cardiovascular-impact-of-sglt2-inhibitors-mechanisms-and-effects
#17
REVIEW
Abdullah Kaplan, Emna Abidi, Ahmed El-Yazbi, Ali Eid, George W Booz, Fouad A Zouein
Diabetes is a global epidemic and a leading cause of death with more than 422 million patients worldwide out of whom around 392 million alone suffer from type 2 diabetes (T2D). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are novel and effective drugs in managing glycemia of T2D patients. These inhibitors gained recent clinical and basic research attention due to their clinically observed cardiovascular protective effects. Although interest in the study of various SGLT isoforms and the effect of their inhibition on cardiovascular function extends over the past 20 years, an explanation of the effects observed clinically based on available experimental data is not forthcoming...
January 11, 2018: Heart Failure Reviews
https://www.readbyqxmd.com/read/29306791/empagliflozin-rescues-diabetic-myocardial-microvascular-injury-via-ampk-mediated-inhibition-of-mitochondrial-fission
#18
Hao Zhou, Shuyi Wang, Pingjun Zhu, Shunying Hu, Yundai Chen, Jun Ren
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria...
December 30, 2017: Redox Biology
https://www.readbyqxmd.com/read/29297732/canagliflozin-and-cardiovascular-and-renal-events-in-type-2-diabetes
#19
Robert Guthrie
Review of: Neal B, Perkovic V, Mahaffey K, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017: 377; 644-657. The report combines the data from two trials, CANVAS and CANVAS-Renal, which were designed to evaluate the safety and effect of canagliflozin, an SGLT-2 inhibitor, on the appearance of cardiovascular and renal events in patients with type 2 diabetes. Enrollees were patients with type 2 diabetes of at least 30 years of age, with a glycated hemoglobin of > or equal to 7...
January 3, 2018: Postgraduate Medicine
https://www.readbyqxmd.com/read/29285511/empagliflozin-reduces-albuminuria-a-promise-for-better-cardiorenal-protection-from-the-empa-reg-outcome-trial
#20
EDITORIAL
Rikke Borg, Frederik Persson
No abstract text is available yet for this article.
December 2017: Annals of Translational Medicine
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