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Canagliflozine

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https://www.readbyqxmd.com/read/29238696/identification-of-clinically-approved-drugs-indacaterol-and-canagliflozin-for-repurposing-to-treat-epidermal-growth-factor-tyrosine-kinase-inhibitor-resistant-lung-cancer
#1
Hongjian Li, Christy Wing-Sum Tong, Yee Leung, Man-Hon Wong, Kenneth Kin-Wah To, Kwong-Sak Leung
In advanced lung cancer, epidermal growth factor tyrosine kinase inhibitors (EGFR TKIs) have extraordinary clinical efficacy. However, their usefulness is severely compromised by drug resistance mediated by various mechanisms, the most important of which is the secondary EGFR T790M mutation. The mutation blocks the binding of EGFR TKIs to the receptor kinase, thereby abolishing the therapeutic efficacy. In this study, we used our free and open-source protein-ligand docking software idock to screen worldwide approved small-molecule drugs against EGFR T790M...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29236983/cardioprotective-anti-hyperglycaemic-medications-a-review-of-clinical-trials
#2
Haitham M Ahmed, Haitham Khraishah, Leslie Cho
Despite extensive clinical efforts to achieve stricter glycaemic control over the past few decades, cardiovascular (CV) disease remains the leading cause of death among diabetic patients. Recently, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor (GLP-1-R) agonists have gained attention due to their apparent effects in reducing CV mortality. Four CV randomized controlled trials: EMPA-REG, CANVAS, LEADER, and SUSTAIN-6, found a decrease in CV events among patients with type 2 diabetes on empagliflozin, canagliflozin, liraglutide, and semaglutide, respectively...
December 9, 2017: European Heart Journal
https://www.readbyqxmd.com/read/29236222/an-indirect-comparison-of-changes-in-the-impact-of-weight-on-quality-of-life-among-subjects-with-type-2-diabetes-treated-with-antihyperglycemic-agents-in-dual-therapy-with-metformin
#3
Shana B Traina, April Slee, Suzy Van Sanden, Joris Diels
INTRODUCTION: It is important to capture the patient experience with a diabetes treatment in clinical trials; however, use of instruments to assess patient-reported outcomes (PROs) in diabetes trials is inconsistent and results may not be reported alongside primary efficacy data. In lieu of head-to-head data, indirect comparisons can be used to compare competing interventions. In this study, we used indirect comparison methods to assess differences in PRO score changes between canagliflozin and other antihyperglycemic agents as add-on to metformin...
December 13, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29227973/will-canagliflozin-lend-credence-to-the-potential-effects-of-sodium-glucose-co-transporter-2-inhibitors-on-renal-endpoints-in-diabetic-nephropathy
#4
Joshua J Neumiller, Connie M Rhee, Kamyar Kalantar-Zadeh
No abstract text is available yet for this article.
December 11, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29226041/dapagliflozin-cardiovascular-safety-and-benefits-in-type-2-diabetes-mellitus
#5
REVIEW
Fatima Saleem
Sodium-glucose co-transporter 2 inhibitors (SGLT2is) such as dapagliflozin, canagliflozin, and empagliflozin, are a promising new therapy in the treatment of type 2 diabetes mellitus (T2DM). SGLT2is can effectively reduce hyperglycemia thus improving glycemic control and they offer some beneficial effects on the cardiovascular (CV) system which can benefit patients with heart failure in addition toT2DM. The United States Food and Drug Administration requires new diabetes mellitus therapies to show a CV safety profile...
October 5, 2017: Curēus
https://www.readbyqxmd.com/read/29205334/sodium-glucose-cotransporter-2-inhibitor-canagliflozin-attenuates-liver-cancer-cell-growth-and-angiogenic-activity-by-inhibiting-glucose-uptake
#6
Kosuke Kaji, Norihisa Nishimura, Kenichiro Seki, Shinya Sato, Soichiro Saikawa, Keisuke Nakanishi, Masanori Furukawa, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Hitoshi Yoshiji
Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells...
December 4, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29197997/class-effects-of-sglt2-inhibitors-in-mouse-cardiomyocytes-and-hearts-inhibition-of-na-h-exchanger-lowering-of-cytosolic-na-and-vasodilation
#7
Laween Uthman, Antonius Baartscheer, Boris Bleijlevens, Cees A Schumacher, Jan W T Fiolet, Anneke Koeman, Milena Jancev, Markus W Hollmann, Nina C Weber, Ruben Coronel, Coert J Zuurbier
AIMS/HYPOTHESIS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) constitute a novel class of glucose-lowering (type 2) kidney-targeted agents. We recently reported that the SGLT2i empagliflozin (EMPA) reduced cardiac cytosolic Na+ ([Na+]c) and cytosolic Ca2+ ([Ca2+]c) concentrations through inhibition of Na+/H+ exchanger (NHE). Here, we examine (1) whether the SGLT2i dapagliflozin (DAPA) and canagliflozin (CANA) also inhibit NHE and reduce [Na+]c; (2) a structural model for the interaction of SGLT2i to NHE; (3) to what extent SGLT2i affect the haemodynamic and metabolic performance of isolated hearts of healthy mice...
December 2, 2017: Diabetologia
https://www.readbyqxmd.com/read/29196150/sglt2-inhibitors-with-cardiovascular-benefits-transforming-clinical-care-in-type2-diabetes-mellitus
#8
REVIEW
Michael d'Emden, John Amerena, Gary Deed, Carol Pollock, Mark E Cooper
Cardiovascular risk reduction in individuals with Type 2 diabetes mellitus (T2DM) is a key part of clinical management. Sodium-glucose co-transporter (SGLT2) inhibitors improve glycaemic control, reduce body weight and decrease blood pressure. In addition, the SGLT2 inhibitors empagliflozin and canagliflozin reduced the risk of composite cardiovascular events in high-risk individuals with T2DM in the EMPA-REG OUTCOME trial and the CANVAS Program, respectively. Empagliflozin also reduced cardiovascular deaths and improved renal outcomes...
November 28, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29193543/initiation-of-dapagliflozin-and-treatment-emergent-fractures
#9
Konstantinos A Toulis, John P Bilezikian, G Neil Thomas, Wasim Hanif, Kalliopi Kotsa, Rasiah Thayakaran, Deepiksana Keerthy, Abd Tahrani, Krishnarajah Nirantharakumar
An increase in the fracture risk was reported in patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin, possibly mediated by effects induced by all members of the sodium-glucose co-transporter 2 inhibitors (SGLT2i) class. It is unclear whether initiation of dapagliflozin is followed by an increase in the risk of fracture. Therefore, we performed a population-based, open cohort study was performed (January 2013-January 2016) using The Health Improvement Network (THIN). 22,618 patients with T2DM (4,548 exposed to dapagliflozin and 18,070 under standard antidiabetic treatment, matched for age and sex) with no history of fractures at baseline...
November 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29183654/-safety-of-sglt2-inhibitors-a-review-of-the-adverse-drug-reactions-registered-in-a-national-database
#10
O Esteban-Jiménez, C Navarro-Pemán, L Urieta-González
OBJECTIVE: To analyse the adverse drug reactions (ADRs) caused by Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) notified in Spain since they have been on the market. MATERIAL AND METHODS: An analysis was made of all the notifications registered in the Spanish Pharmacovigilance System of drugs for human use, arising from the use of SGLT2i. RESULTS: A total of 311 notifications were recorded, of which 169 (54.34%) were related to dapagliflozin, 81 (26...
November 25, 2017: Semergen
https://www.readbyqxmd.com/read/29174031/acute-renal-failure-with-sodium-glucose-cotransporter-2-inhibitors-analysis-of-the-fda-adverse-event-report-system-database
#11
A Perlman, S N Heyman, I Matok, J Stokar, M Muszkat, A Szalat
BACKGROUND AND AIMS: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. METHODS AND RESULTS: We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016...
December 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29172834/managing-and-maintaining-bone-mineral-density-in-diabetes-patients-with-pharmacotherapy
#12
C Y Fixen, Danielle R Fixen
The population of patients with osteoporosis and diabetes is increasing as the aging population increases. Loss of bone mineral density occurs in patients with diabetes but is not always a priority in the practice setting. The aim of this review is to discuss clinical considerations when managing osteoporosis in patients with diabetes. Areas covered: The pathophysiology of decreased bone mineral density in patients with diabetes is discussed. Additionally, diabetic risk factors for fracture, such as hypoglycemia, the National Osteoporosis Foundation recommendations for osteoporosis, and secondary causes of osteoporosis, including disease and medication related causes, are discussed...
November 27, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29168387/impacts-of-sodium-glucose-co-transporter-type-2-inhibitors-on-central-blood-pressure
#13
Tsuneo Takenaka, Yoichi Ohno, Hiromichi Suzuki
AIMS: To assess the effects of sodium-glucose co-transporter type 2 inhibitors on central blood pressure, an important determinant of cardiovascular events. METHODS: Canagliflozin, Empagliflozin or Luseogliflozin was given for 102 type 2 diabetic patients with hypertension and nephropathy. Central blood pressure was evaluated by radial tonometry. Clinical parameters were followed for 6 months. RESULTS: Three differing sodium-glucose co-transporter type 2 inhibitors similarly reduced brachial and central blood pressures, casual blood sugar, haemoglobin A1c, estimated glomerular filtration rate and albuminuria without significant changes in pulse rate and lipid profiles...
November 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/29167170/canagliflozin-reduces-plasma-uremic-toxins-and-alters-the-intestinal-microbiota-composition-in-a-chronic-kidney-disease-mouse-model
#14
Eikan Mishima, Shinji Fukuda, Yoshitomi Kanemitsu, Daisuke Saigusa, Chikahisa Mukawa, Kei Asaji, Yotaro Matsumoto, Hiroki Tsukamoto, Tatsuki Tachikawa, Tomoya Tsukimi, Noriko N Fukuda, Hsin-Jung Ho, Koichi Kikuchi, Chitose Suzuki, Fumika Nanto, Takehiro Suzuki, Sadayoshi Ito, Tomoyoshi Soga, Yoshihisa Tomioka, Takaaki Abe
Accumulation of uremic toxins, which exert deleterious effects in chronic kidney disease, is influenced by the intestinal environment; the microbiota contributes to the production of representative uremic toxins including p-cresyl sulfate and indoxyl sulfate. Canagliflozin is a sodium/glucose co-transporter (SGLT) 2 inhibitor, and it also exerts a modest inhibitory effect on SGLT1. The inhibition of intestinal SGLT1 can influence the gastrointestinal environment. We examined the effect of canagliflozin on the accumulation of uremic toxins in chronic kidney disease using adenine-induced renal failure mice...
November 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29166232/canagliflozin-and-cardiovascular-and-renal-events-in-type-2-diabetes
#15
LETTER
Bruce Neal, Vlado Perkovic, David R Matthews
New England Journal of Medicine, Volume 377, Issue 21, Page 2097-2099, November 2017.
November 23, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/29165885/the-association-between-the-dosage-of-sglt2-inhibitor-and-weight-reduction-in-type-2-diabetes-patients-a-meta-analysis
#16
Xiaoling Cai, Wenjia Yang, Xueying Gao, Yifei Chen, Lingli Zhou, Simin Zhang, Xueyao Han, Linong Ji
OBJECTIVE: Sodium glucose cotransporter 2 (SGLT2) inhibitors may induce urinary glucose excretion via the inhibition of renal glucose reabsorption, improve glycemic control, and lower body weight. The aim of this meta-analysis was to evaluate weight changes in patients who received different dosages of SGLT2 inhibitors. METHODS: Overall, 55 placebo-controlled trials were included. RESULTS: The results indicated that treatment with 2.5 mg, 5 mg, 10 mg, and 20 mg of dapagliflozin led to significant decreases in body weight compared with a placebo (weighted mean difference [WMD], -1...
November 22, 2017: Obesity
https://www.readbyqxmd.com/read/29165869/canagliflozin-stability-study-and-eco-friendly-chromatographic-determination-of-its-degradation-product-a-comparative-study
#17
Aml A Emam
Canagliflozin is a newly approved drug for type II diabetes mellitus. A full stability study of Canagliflozin was performed following international conference on harmonization strategies. The drug was stable against all conditions except oxidation where only one degradation product was separated and structurally elucidated using mass spectrometry and IR spectroscopy. A green high-performance thin-layer chromatographic densitometric determination was developed and validated for the accurate quantification of Canagliflozin and its main oxidative degradation product...
November 22, 2017: Journal of Separation Science
https://www.readbyqxmd.com/read/29162781/successful-withdrawal-from-dobutamine-by-canagliflozin-in-a-diabetic-patient-with-stage-d-heart-failure
#18
Masaki Nakagaito, Shuji Joho, Ryuichi Ushijima, Makiko Nakamura, Tadakazu Hirai, Koichiro Kinugawa
Patients with stage D heart failure (HF) frequently become dependent on high doses of diuretics and inotropic agents. Recently, a sodium-glucose cotransporter 2 inhibitor (SGLT2i), an oral antidiabetic agent, has been demonstrated to have favorable effects in preventing HF. However, it remains unknown whether SGLT2i is reliable for patients with decompensated HF. We experienced a case of a patient with stage D HF for whom attempting intravenous dobutamine withdrawal was difficult even after the administration of all conventional pharmacological treatment...
November 22, 2017: International Heart Journal
https://www.readbyqxmd.com/read/29154404/diabetes-news
#19
Ann M Carracher, Payal H Marathe, Kelly L Close
The 20th annual Diabetes Canada Professional Conference took place in November 2017 in Edmonton, Alberta, Canada, featuring Dr Daniel Drucker on 30 years of incretin biology research and Dr David Matthews on implications of the Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS) trial,(1) among other sessions.
November 20, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/29144539/model-based-evaluation-of-proximal-sodium-reabsorption-through-sglt2-in-health-and-diabetes-and-the-effect-of-inhibition-with-canagliflozin
#20
Jessica A Brady, K Melissa Hallow
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce glucose levels in diabetes by inhibiting renal glucose reabsorption in the proximal tubule (PT), resulting in urinary glucose excretion. A recent large cardiovascular outcomes trial suggested that the SGLT2i empagliflozin may also decrease risk of renal dysfunction. Because sodium (Na) and glucose reabsorption are coupled through SGLT2, it is hypothesized that the renal benefits may be derived from lowering Na reabsorption in the PT, which would lead to favorable renal hemodynamic changes...
November 16, 2017: Journal of Clinical Pharmacology
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