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Dapagliflozine

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https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#1
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29141939/dapagliflozin-in-focal-segmental-glomerulosclerosis-a-combined-human-rodent-pilot-study
#2
Harindra Rajasekeran, Heather N Reich, Michelle A Hladunewich, Daniel Cattran, Julie A Lovshin, Yuliya Lytvyn, Petter Bjornstad, Vesta Lai, Josephine Tse, Leslie Cham, Syamantak Majumder, Bridgit B Bowskill, M Golam Kabir, Suzanne L Advani, Ian W Gibson, Manish M Sood, Andrew Advani, David Z I Cherney
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is an important cause of non-diabetic chronic kidney disease (CKD). Sodium glucose cotransporter-2 inhibition (SGLT2i) therapy attenuates the progression of diabetic nephropathy, but it remains unclear whether SGLT2i provides renoprotection in non-diabetic CKD such as FSGS. OBJECTIVE: The primary aim of this pilot study was to determine the effect of 8 weeks of dapagliflozin on GFR in humans and in experimental FSGS...
November 15, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29134558/development-of-hyperkalemia-following-treatment-with-dapagliflozin-dapa-in-a-patient-with-type-2-diabetes-after-bilateral-adrenalectomy
#3
Daichi Miyaoka, Akihiro Tsuda, Noriyuki Hayashi, Norikazu Toi, Akiyo Yamasaki, Yuki Nagata, Shinya Nakatani, Masafumi Kurajoh, Shinsuke Yamada, Tomoaki Morioka, Yasuo Imanishi, Masanori Emoto, Masaaki Inaba
Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is known to have a beneficial diuretic effect, in addition to a glucose-lowering effect. Although SGLT2 inhibitor has been reported, the increase of hyperkalemia in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors, their mechanism of action is unclear. We report the first case of a type 2 diabetes (T2DM) patient with potential mineralocorticoid deficiency who developed hyperkalemia after administration of DAPA...
November 13, 2017: CEN Case Reports
https://www.readbyqxmd.com/read/29132354/correction-to-dapagliflozin-decreases-small-dense-low-density-lipoprotein-cholesterol-and-increases-high-density-lipoprotein-2-cholesterol-in-patients-with-type-2-diabetes-comparison-with-sitagliptin
#4
Toshiyuki Hayashi, Tomoyasu Fukui, Noriko Nakanishi, Saki Yamamoto, Masako Tomoyasu, Anna Osamura, Makoto Ohara, Takeshi Yamamoto, Yasuki Ito, Tsutomu Hirano
Following publication of the original article [1], the authors identified a number of errors. In Result (P.3), Table 1 (P.4), Table 5 (P.9) and Supplementary Table 1, the correct unit for adiponectin was μg/mL. In Table 1 (P.4), the correct value for the post treatment body weight in dapagliflozin was 76.2±14.8. In Table 6 (P.10), the correct value for the pre treatment sd LDL/LDL-C in decreased LDL-C group was 0.38±0.10.
November 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29127652/dapagliflozin-as-a-cause-of-acute-tubular-necrosis-with-heavy-consequences-a-case-report
#5
Christos Pleros, Elisavet Stamataki, Antonia Papadaki, Nikolaos Damianakis, Rafaela Poulidaki, Charikleia Gakiopoulou, Ioannis Tzanakis
A 50-year-old man with type II diabetes, hypertension and dyslipidemia, presented with non-oliguric acute kidney injury (AKI) and anemia. Renal biopsy showed acute tubular necrosis (ATN) with extensive cytoplasmic vacuolization and areas of tubulitis. These findings were ultimately attributed to dapagliflozin, which he started 3 months earlier due to poor glycemic control. ATN with similar microscopic findings has been described with larger doses of dapagliflozin in non-clinical trials. Our patient was started on dialysis and remained dialysis-dependent for 4 weeks while his renal function improved gradually thereafter...
November 10, 2017: CEN Case Reports
https://www.readbyqxmd.com/read/29074329/degree-of-ketonaemia-and-its-association-with-insulin-resistance-after-dapagliflozin-treatment-in-type-2-diabetes
#6
S H Min, T J Oh, S-I Baek, D-H Lee, K M Kim, J H Moon, S H Choi, K S Park, H C Jang, S Lim
BACKGROUND: Euglycaemic ketoacidosis has been reported after sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. However, the degree of ketonaemia and its metabolic effects have not been well investigated. Our study examined the degree of ketonaemia induced by SGLT2 inhibition and its association with metabolic profiles in type 2 diabetes mellitus (T2DM). METHODS: Biochemical parameters, including insulin, glucagon, free fatty acid (FFA), β-hydroxybutyrate (BHB) and acetoacetate (ACA) levels, were measured in 119 T2DM patients after dapagliflozin treatment for>3 months, and compared with a matched control group...
October 23, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/29061124/dapagliflozin-acutely-improves-endothelial-dysfunction-reduces-aortic-stiffness-and-renal-resistive-index-in-type-2-diabetic-patients-a-pilot-study
#7
Anna Solini, Livia Giannini, Marta Seghieri, Edoardo Vitolo, Stefano Taddei, Lorenzo Ghiadoni, Rosa Maria Bruno
BACKGROUND: Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms. METHODS: Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12...
October 23, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29029092/corrigendum-for-dapagliflozin-lowers-plasma-glucose-concentration-and-improves-%C3%AE-cell-function
#8
(no author information available yet)
No abstract text is available yet for this article.
October 5, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29024278/why-do-sglt2-inhibitors-reduce-heart-failure-hospitalization-a-differential-volume-regulation-hypothesis
#9
REVIEW
K Melissa Hallow, Gabriel Helmlinger, Peter J Greasley, John J V McMurray, David W Boulton
The effect of a sodium glucose cotransporter 2 inhibitor (SGLT2i) in reducing heart failure hospitalization in the EMPA-REG OUTCOMES trial has raised the possibility of using these agents to treat established heart failure. We hypothesize that osmotic diuresis induced by SGLT2 inhibition, a distinctly different diuretic mechanism than other diuretic classes, results in greater electrolyte-free water clearance, and ultimately in greater fluid clearance from the interstitial fluid (IF) space than from the circulation, potentially resulting in congestion relief with minimal impact on blood volume, arterial filling, and organ perfusion...
October 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29016744/novel-effects-of-dapagliflozin-on-epicardial-adipose-tissue-with-insulin-resistance-high-levels-of-inflammatory-chemokines-production-and-low-differentiation-ability
#10
Esther Díaz-Rodríguez, Rosa M Agra, Ángel L Fernández, B Adrio, Tomás García-Caballero, José R González-Juanatey, Sonia Eiras
Aims: In patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, high pro-inflammatory chemokines and low differentiation ability. Since dapagliflozin reduces body fat and cardiovascular events in diabetic patients, we wanted to know its effect on EAT and subcutaneous adipose tissue (SAT). Methods and results: Adipose samples were obtained from 52 patients undergoing heart surgery. Sodium-glucose cotransporter 2 (SGLT2) expression was determined by real time PCR (n = 20), Western blot and immunohistochemistry...
September 11, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28984487/dapagliflozin-and-saxagliptin-tablets-for-adults-with-type-2-diabetes
#11
André J Scheen
Saxagliptin (a dipeptidyl peptidase-4 inhibitor, DPP-4i) and dapagliflozin (a sodium-glucose cotransporter type 2 inhibitor, SGLT2i) improve glucose control in type 2 diabetes (T2D) through different potentially complementary mechanisms, thus offering the opportunity for a combined therapy. Area covered: The characteristics of the saxagliptin/dapagliflozin combination are analysed, focusing on: 1) pharmacokinetic and pharmacodynamic properties; 2) efficacy and safety in phase III trials with concurrent and sequential add-on therapy; and 3) potential use in clinical practice, including in special populations (cardiovascular disease, heart failure, chronic kidney disease, elderly)...
October 18, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28977090/use-of-sglt-2-inhibitors-in-the-treatment-of-type-2-diabetes-mellitus
#12
REVIEW
Leyna Leite Santos, Fernando José Camello de Lima, Célio Fernando de Sousa-Rodrigues, Fabiano Timbó Barbosa
INTRODUCTION: Diabetes mellitus is one of the most common chronic diseases in the world, with high morbidity and mortality rates, resulting in a greatly negative socioeconomic impact. Although there are several classes of oral antidiabetic agents, most of the patients are outside the therapeutic goal range. OBJECTIVE: To review the use of SGLT-2 inhibitors in the treatment of type 2 diabetes mellitus, focusing on their favorable and unfavorable effects, as well as on cardiovascular profile...
July 2017: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/28976221/dapagliflozin-attenuates-human-vascular-endothelial-cell-activation-and-induces-vasorelaxation-a-potential-mechanism-for-inhibition-of-atherogenesis
#13
Tracey Gaspari, Iressa Spizzo, HongBin Liu, Yunshan Hu, Richard W Simpson, Robert E Widdop, Anthony E Dear
BACKGROUND: Sodium glucose transporter type 2 inhibitors may reduce cardiovascular events in type 2 diabetes. Our study aimed to determine the effect of the sodium glucose transporter type 2 inhibitor dapagliflozin on endothelial cell activation, vasoreactivity and atherogenesis using in vitro and in vivo models and identify associated molecular mechanisms. METHODS: In vitro studies utilised human vascular endothelial cells stimulated with tumour necrosis factor α or hyperglycaemic conditions...
October 1, 2017: Diabetes & Vascular Disease Research
https://www.readbyqxmd.com/read/28967594/rationale-and-design-of-the-darwin-t2d-dapagliflozin-real-world-evidence-in-type-2-diabetes-a-multicenter-retrospective-nationwide-italian-study-and-crowdsourcing-opportunity
#14
G P Fadini, G Zatti, A Consoli, E Bonora, G Sesti, A Avogaro
BACKGROUND: Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. AIMS: We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society...
August 8, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28950419/dapagliflozin-in-patients-with-type-2-diabetes-mellitus-a-pooled-analysis-of-safety-data-from-phase-iib-iii-clinical-trials
#15
Serge Jabbour, Jochen Seufert, Andre Scheen, Clifford J Bailey, Cathrina Karup, Anna M Langkilde
AIM: To evaluate the safety and tolerability of dapagliflozin, a highly selective sodium-glucose co-transporter-2 inhibitor, in patients with type 2 diabetes mellitus (T2DM). METHODS: Data were pooled from 13 placebo-controlled trials of up to 24 weeks' duration (dapagliflozin, n = 2360; placebo, n = 2295). Larger placebo-/comparator-controlled pools of 21 (≤208 weeks; dapagliflozin, n = 5936; control, n = 3403) and 30 trials (≥12 weeks; dapagliflozin, n = 9195; control, n = 4629) assessed the rare adverse events (AEs) of diabetic ketoacidosis (DKA) and lower limb amputation, respectively...
September 26, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28948541/cost-of-glycemic-target-achievement-with-sodium-glucose-co-transporter-2-inhibitors-in-patients-with-type-2-diabetes-in-the-uk
#16
Marc Evans, Sayeed Achha, Cheryl Neslusan
INTRODUCTION: Diabetes-related costs make up a large portion of healthcare expenditures in the UK. Many of these costs are related to treatment of diabetes-related complications. Reducing HbA1c to <7.0% (53 mmol/mol) reduces the incidence of complications and comorbidities. Metformin plus sulfonylurea is the most common dual oral combination therapy in the UK. The costs of achieving HbA1c <7.0% in patients inadequately controlled on metformin plus sulfonylurea were analyzed for the sodium glucose co-transporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin from the perspective of the UK National Health System...
October 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28926495/bolstering-your-armamentarium-with-sglt2-inhibitors
#17
Lucia M Novak, Davida F Kruger
Sodium-glucose cotransporter-2 inhibitors have a unique mechanism of action in the kidneys that causes glucosuria, which lowers plasma glucose. They are also associated with reduced body weight and BP, and a low incidence of hypoglycemia. This article reviews the pharmacologic profiles and clinical implications of canagliflozin, dapagliflozin, and empagliflozin.
October 18, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28924948/magnetic-nanoparticles-for-the-delivery-of-dapagliflozin-to-hypoxic-tumors-physicochemical-characterization-and-cell-studies
#18
Athina Angelopoulou, Efstathia Voulgari, Argiris Kolokithas-Ntoukas, Aristides Bakandritsos, Konstantinos Avgoustakis
In solid tumors, hypoxia (lack of oxygen) is developed, which leads to the development of resistance of tumor cells to chemotherapy and radiotherapy through various mechanisms. Nevertheless, hypoxic cells are particularly vulnerable when glycolysis is inhibited. For this reason, in this study, the development of magnetically targetable nanocarriers of the sodium-glucose transporter protein (SGLT2) inhibitor dapagliflozin (DAPA) was developed for the selective delivery of DAPA in tumors. This nanomedicine in combination with radiotherapy or chemotherapy should be useful for effective treatment of hypoxic tumors...
September 18, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28919061/efficacy-and-safety-of-dapagliflozin-in-patients-with-inadequately-controlled-type-1-diabetes-depict-1-24-week-results-from-a-multicentre-double-blind-phase-3-randomised-controlled-trial
#19
Paresh Dandona, Chantal Mathieu, Moshe Phillip, Lars Hansen, Steven C Griffen, Diethelm Tschöpe, Fredrik Thorén, John Xu, Anna Maria Langkilde
BACKGROUND: Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. METHODS: DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18-75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment...
September 13, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28912902/effects-of-dapagliflozin-on-body-composition-and-liver-tests-in-patients-with-nonalcoholic-steatohepatitis-associated-with-type-2-diabetes-mellitus-a-prospective-open-label-uncontrolled-study
#20
Hiroshi Tobita, Shuichi Sato, Tatsuya Miyake, Shunji Ishihara, Yoshikazu Kinoshita
BACKGROUND: Nonalcoholic steatohepatitis (NASH) is an active form of nonalcoholic fatty liver disease. Risk factors for NASH include type 2 diabetes mellitus (T2DM) and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitors used to treat T2DM prevent glucose reabsorption in the kidney and increase glucose urinary excretion. Dapagliflozin is a potent, selective SGLT2 inhibitor that reduces hyperglycemia in patients with T2DM and has been demonstrated to reduce some complications associated with NASH in rodent models...
2017: Current Therapeutic Research, Clinical and Experimental
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