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Canagliflozin

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https://www.readbyqxmd.com/read/29168387/impacts-of-sodium-glucose-co-transporter-type-2-inhibitors-on-central-blood-pressure
#1
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
#2
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
#3
(no author information available yet)
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
#4
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
#5
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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/29134712/characterization-of-forced-degradation-products-of-canagliflozine-by-lc-qtof-ms-ms-and-in-silico-toxicity-predictions
#9
Shandilya Mahamuni Baira, Pradipbhai D Kalariya, Rakesh Nimbalkar, Prabha Garg, R Srinivas, M V N Kumar Talluri
RATIONALE: Forced degradation studies are useful for better understanding of the stability of active pharmaceutical ingredients and drugs and to generate information about drug degradation pathways and formation of degradation products (DPs). Identification of DPs plays a vital role in establishing the safety and therapeutic benefit of the drug. METHODS: Canagliflozin (CAN) was subjected to different stress conditions as per ICH guidelines (Q1A R2). All the DPs and the drug were well separated on Aquity CSH C18 (100 × 2...
November 14, 2017: Rapid Communications in Mass Spectrometry: RCM
https://www.readbyqxmd.com/read/29133607/cardiovascular-outcomes-and-risks-after-initiation-of-a-sodium-glucose-co-transporter-2-inhibitor-results-from-the-easel-population-based-cohort-study
#10
Jacob A Udell, Zhong Yuan, Toni Rush, Nicholas M Sicignano, Michael Galitz, Norman Rosenthal
Background : Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose co-transporter 2 inhibitors (SGLT2i). Trials may have limited ability to address individual endpoints or safety concerns. Methods : We performed a population-based cohort study among type 2 diabetes patients with established cardiovascular disease newly initiated on antihyperglycemic agents (AHAs) within the US Department of Defense Military Health System between 4/1/2013 and 12/31/2016. Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite endpoint of all-cause mortality (ACM) and hospitalization for heart failure (HHF) event, major adverse cardiovascular events (MACE; defined as ACM, nonfatal myocardial infarction, and nonfatal stroke), and individual endpoints were evaluated using conditional Cox models comparing new SGLT2i users with other AHAs...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29133604/canagliflozin-for-primary-and-secondary-prevention-of-cardiovascular-events-results-from-the-canvas-program-canagliflozin-cardiovascular-assessment-study
#11
Kenneth W Mahaffey, Bruce Neal, Vlado Perkovic, Dick de Zeeuw, Greg Fulcher, Ngozi Erondu, Wayne Shaw, Elisa Fabbrini, Tao Sun, Qiang Li, Mehul Desai, David R Matthews
BACKGROUND : Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk. The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation. METHODS : The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29133603/canagliflozin-cui-bono
#12
Matthew A Cavender, Mikhail Kosiborod
Cardiovascular disease accounts for the majority of excess deaths seen in patients with Type 2 diabetes (T2D).(1) Thus, in order to improve outcomes in this population, clinicians should focus on therapies that decrease the risk of subsequent cardiovascular events. Over the last two years, randomized controlled clinical trials have identified several agents that decrease cardiovascular events in patients with T2D with or at high risk for cardiovascular disease (CVD) - effects likely unrelated to glucose-lowering, the indication for which they were originally developed...
November 13, 2017: Circulation
https://www.readbyqxmd.com/read/29127736/liver-x-receptor-activation-inhibits-sglt2-mediated-glucose-transport-in-human-renal-proximal-tubular-cells
#13
Pattira Chonlaket, Teerasak Wongwan, Sunhapas Soodvilai
Liver X receptors (LXRs) are members of a nuclear receptor family consisting of two isoforms, LXR-α and LXR-β. They play a major role in energy metabolism including lipid and glucose metabolism. Recent studies reported LXRs regulate plasma glucose although the mechanism is still uncertain. The present study investigated whether LXR activation regulates sodium glucose cotransporter2 (SGLT2) in human renal proximal tubular cells. LXR agonists, T0901317 and GW3965, inhibited SGLT2-mediated glucose uptake in concentration-dependent manners...
November 11, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/29110384/long-term-efficacy-and-safety-of-canagliflozin-in-combination-with-insulin-in-japanese-patients-with-type-2-diabetes-mellitus
#14
Nobuya Inagaki, Shin-Ichi Harashima, Kohei Kaku, Kazuoki Kondo, Nobuko Maruyama, Makiko Otsuka, Yutaka Kawaguchi, Hiroaki Iijima
AIM: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. MATERIALS AND METHODS: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N=70) or canagliflozin (100 mg, CAN; N=76), followed by a 36-week open-label period in which all patients received canagliflozin...
November 7, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29109617/euglycemic-diabetic-ketoacidosis-accompanied-by-severe-hypophosphatemia-during-recovery-in-a-patient-with-type-2-diabetes-being-treated-with-canagliflozin-metformin-combination-therapy
#15
Sonia Shoukat, Nida Arshad Usmani, Oluwakemi Soetan, Faisal Qureshi
No abstract text is available yet for this article.
October 2017: Clinical Diabetes: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29103664/canagliflozin-in-conjunction-with-sulfonylurea-maintains-glycemic-control-and-weight-loss-over-52-weeks-a-randomized-controlled-trial-in-patients-with-type-2-diabetes-mellitus
#16
Jean-François Yale, John Xie, Stephen E Sherman, Claude Garceau
PURPOSE: Our aim was to investigate the long-term efficacy and safety of canagliflozin, a sodium-glucose co-transporter 2 inhibitor, added to background sulfonylurea (SU) monotherapy for patients with type 2 diabetes mellitus. METHODS: The CANagliflozin cardioVascularAssessment Study (CANVAS) was a double-blind, placebo-controlled cardiovascular outcomes study that randomly assigned participants to receive placebo or canagliflozin 100 or 300 mg once daily in addition to routine therapy...
November 2, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/29076040/sglt2-inhibitors-through-the-windows-of-empa-reg-and-canvas-trials-a-review
#17
REVIEW
Ashu Rastogi, Anil Bhansali
EMPA-REG OUTCOME and CANVAS trials were designed to study the cardiovascular safety of empagliflozin and canagliflozin, respectively. Both studies were sufficiently powered to study the non-inferiority for cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (DM) and showed superiority for major adverse cardiovascular events and composite renal outcomes independent of glycemic control. Further, all patients in EMPA-REG had prior CV events (secondary prevention), compared to CANVAS that also included subjects with no prior CV events, indicating the beneficial effects of canagliflozin in primary prevention of CV events as well...
December 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29068709/altered-patterns-of-early-metabolic-decompensation-in-type-1-diabetes-during-treatment-with-a-sglt2-inhibitor-an-insulin-pump-suspension-study
#18
Neha S Patel, Michelle A Van Name, Eda Cengiz, Lori R Carria, Stuart A Weinzimer, William V Tamborlane, Jennifer L Sherr
BACKGROUND: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. METHODS: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7...
November 2017: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/29063509/erratum-to-efficacy-of-additional-canagliflozin-administration-to-type-2-diabetes-patients-receiving-insulin-therapy-examination-of-diurnal-glycemic-patterns-using-continuous-glucose-monitoring-cgm
#19
Mihoko Matsumura, Yuki Nakatani, Seiichi Tanka, Chie Aoki, Masaaki Sagara, Kazunori Yanagi, Kunihiro Suzuki, Yoshimasa Aso
Unfortunately, the original publication of this paper contained errors in the presentation of Fig. 2.
October 23, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29061576/sodium-glucose-cotransporter-2-inhibition-in-heart-failure-potential-mechanisms-clinical-applications-and-summary-of-clinical-trials
#20
REVIEW
Yuliya Lytvyn, Petter Bjornstad, Jacob A Udell, Julie A Lovshin, David Z I Cherney
Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor...
October 24, 2017: Circulation
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