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Dapagliflozine

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https://www.readbyqxmd.com/read/28544884/a-validated-uhplc-qtof-ms-method-for-quantification-of-metformin-and-teneligliptin-in-rat-plasma-application-to-pharmacokinetic-interaction-study
#1
David Paul, Lingesh Allakonda, Nanjappan Satheeshkumar
In this study a sensitive UHPLC-QTOF-MS method was developed and validated for the quantitation of the metformin (MET) and teneligliptin (TEN) in rat plasma using dapagliflozin as an internal standard (IS). Chromatographic separation were carried out on a Acquity UPLC HSS Cyano column (100mm x 2.1mm, 1.8μm) using gradient mobile phase system consisting of 0.1% formic acid and acetonitrile at a flow rate of 0.4mL/min, within a run time of 6min. Protein precipitation method was used as sample preparation approach...
May 15, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28536217/caution-advised-with-dapagliflozin-in-the-setting-of-male-urinary-tract-outlet-obstruction
#2
Victoria Hall, Jason Kwong, Douglas Johnson, Elif Ilhan Ekinci
We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community...
May 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28535688/sglt-2-inhibitors-is-there-a-role-in-type-1-diabetes-mellitus-management
#3
Nabila Ahmed-Sarwar, Angela K Nagel, Samantha Leistman, Kevin Heacock
OBJECTIVE: The purpose of this review is to identify and evaluate disease management of patients with type 1 diabetes mellitus (T1DM) who were treated with a sodium-glucose cotransporter 2 (SGLT-2) inhibitor as an adjunct to insulin therapy. DATA SOURCES: A PubMed (1969 to March 2017) and Ovid (1946 to March 2017) search was performed for articles published utilizing the following MESH terms: canagliflozin, empagliflozin, dapagliflozin, type 1 diabetes mellitus, insulin dependent diabetes, insulin, sodium-glucose transporter 2...
May 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28526179/empa-reg-outcome-the-nephrologist-s-point-of-view
#4
Christoph Wanner
There is increasing evidence that sodium glucose cotransporter 2 (SGLT2) inhibitors have renoprotective effects, as demonstrated by the renal analyses from clinical trials including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME), CANagliflozin Treatment And Trial Analysis versus SUlphonylurea (CANTATA-SU), and the dapagliflozin renal study. The potential mechanisms responsible are likely multifactorial, and direct renovascular and hemodynamic effects are postulated to play a central role...
May 16, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28522450/lower-risk-of-heart-failure-and-death-in-patients-initiated-on-sglt-2-inhibitors-versus-other-glucose-lowering-drugs-the-cvd-real-study
#5
Mikhail Kosiborod, Matthew A Cavender, Alex Z Fu, John P Wilding, Kamlesh Khunti, Reinhard W Holl, Anna Norhammar, Kåre I Birkeland, Marit Jørgensen, Marcus Thuresson, Niki Arya, Johan Bodegård, Niklas Hammar, Peter Fenici
Background -Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose co-transporter-2 inhibitor (SGLT-2i) empagliflozin in type 2 diabetes patients with atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose lowering drugs (oGLDs) in six countries to determine if these benefits are seen in real-world practice, and across SGLT-2i class. Methods -Data were collected via medical claims, primary care/hospital records and national registries from the US, Norway, Denmark, Sweden, Germany and the UK...
May 18, 2017: Circulation
https://www.readbyqxmd.com/read/28506912/characterization-and-comparison-of-sglt2-inhibitors-part-3-effects-on-diabetic-complications-in-type-2-diabetic-mice
#6
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28504650/neutrophil-derived-s100-calcium-binding-proteins-a8-a9-promote-reticulated-thrombocytosis-and-atherogenesis-in-diabetes
#7
Michael J Kraakman, Man K S Lee, Annas Al-Sharea, Dragana Dragoljevic, Tessa J Barrett, Emilie Montenont, Debapriya Basu, Sarah Heywood, Helene L Kammoun, Michelle Flynn, Alexandra Whillas, Nordin M J Hanssen, Mark A Febbraio, Erik Westein, Edward A Fisher, Jaye Chin-Dusting, Mark E Cooper, Jeffrey S Berger, Ira J Goldberg, Prabhakara R Nagareddy, Andrew J Murphy
Platelets play a critical role in atherogenesis and thrombosis-mediated myocardial ischemia, processes that are accelerated in diabetes. Whether hyperglycemia promotes platelet production and whether enhanced platelet production contributes to enhanced atherothrombosis remains unknown. Here we found that in response to hyperglycemia, neutrophil-derived S100 calcium-binding proteins A8/A9 (S100A8/A9) interact with the receptor for advanced glycation end products (RAGE) on hepatic Kupffer cells, resulting in increased production of IL-6, a pleiotropic cytokine that is implicated in inflammatory thrombocytosis...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28502502/dapagliflozin-in-patients-with-type-ii-diabetes-mellitus-with-and-without-elevated-triglyceride-and-reduced-high-density-lipoprotein-cholesterol-levels
#8
Harold E Bays, Peter Sartipy, John Xu, Carl David Sjöström, James A Underberg
BACKGROUND: Dapagliflozin is a selective sodium-glucose cotransporter 2 inhibitor that improves glycemic control in patients with type II diabetes mellitus (T2DM) by reducing renal glucose reabsorption. OBJECTIVE: The aim was to evaluate the lipid effects of dapagliflozin 10 mg or placebo in patients with T2DM with/without baseline elevated triglyceride and reduced high-density lipoprotein (HDL) cholesterol levels. METHODS: This was a post hoc analysis of 10 phase 3, placebo-controlled studies of dapagliflozin 10 mg (N = 2237) or placebo (N = 2164) administered for 24 weeks in patients with T2DM...
March 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28499695/dapagliflozin-modulates-glucagon-secretion-in-an-sglt2-independent-manner-in-murine-alpha-cells
#9
A Solini, G Sebastiani, L Nigi, E Santini, C Rossi, F Dotta
AIM: SGLT2 inhibitors reduce renal glucose uptake through an insulin-independent mechanism. They also increase glucagon concentration, although the extent to which this is due to a direct effect on pancreatic alpha cells remains unclear. METHODS: In the present work, αTC1 cells treated with the SGLT2 inhibitor dapagliflozin (Dapa) were analyzed for glucose transporters, molecular mediators of hormone secretion, glucagon and GLP-1 release, and the effects of somatostatin...
May 9, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28447181/sglt-2-inhibition-with-dapagliflozin-reduces-the-activation-of-the-nlrp3-asc-inflammasome-and-attenuates-the-development-of-diabetic-cardiomyopathy-in-mice-with-type-2-diabetes-further-augmentation-of-the-effects-with-saxagliptin-a-dpp4-inhibitor
#10
Yumei Ye, Mandeep Bajaj, Hsiu-Chiung Yang, Jose R Perez-Polo, Yochai Birnbaum
PURPOSE: We assessed whether (1) dapagliflozin (Dapa, an SGLT2-inhibitor) attenuates the deterioration of heart function Nlrp3 and inflammasome activation in diabetic mice. (2) The effects can be augmented with saxagliptin (Saxa), a DDP4-inhibitor. (3) Dapa effect is possibly SGLT2-independent on cardiofibroblasts in vitro. METHODS: Type 2 diabetic (BTBR ob/ob) and wild-type (WT) mice received vehicle, Dapa, or Dapa+Saxa for 8 weeks. Glucose tolerance test and echocardiogram were performed...
April 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28447076/promising-cardiovascular-and-blood-pressure-effects-of-the-sglt2-inhibitors-a-new-class-of-antidiabetic-drugs
#11
S G Chrysant
Patients with type 2 diabetes mellitus (T2DM) exhibit an increased risk of cardiovascular (CV) events. Treatment of these patients with traditional as well as newer glucose-lowering drugs has not demonstrated superiority in CV outcomes compared to placebo, despite effective control of diabetes. However, the recently FDA-approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for the treatment of T2DM have demonstrated promising CV-protecting and blood pressure-lowering effects in addition to their effectiveness in glucose lowering, making them a novel class of drugs for the treatment of T2DM...
March 2017: Drugs of Today
https://www.readbyqxmd.com/read/28440590/sodium-glucose-co-transporter-2-sglt2-inhibitors-and-fracture-risk-in-patients-with-type-2-diabetes-mellitus-a-meta-analysis
#12
Darin Ruanpeng, Patompong Ungprasert, Jutarat Sangtian, Tasma Harindhanavudhi
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors could potentially alter calcium and phosphate homeostasis and may increase the risk of bone fracture. METHODS: The current meta-analysis was conducted to investigate the fracture risk among patients with type 2 diabetes mellitus treated with SGLT2 inhibitors. Randomized controlled trials that compared the efficacy of SGLT2 inhibitors to placebo were identified. The risk ratios of fracture among patients who received SGLT2 inhibitors versus placebo were extracted from each study...
April 25, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28440009/sodium-glucose-co-transporter-2-inhibitors-for-type-2-diabetes-mellitus-an-overview-for-the-primary-care-physician
#13
REVIEW
Paresh Dandona, Ajay Chaudhuri
AIMS: Sodium-glucose co-transporter type 2 (SGLT2) inhibitors are a new class of anti-hyperglycaemic agents in type 2 diabetes mellitus (T2DM). This review examines their mechanism of action and provides an overview of safety and efficacy from the main studies of SGLT2 inhibitors marketed in the United States and Europe, namely, canagliflozin, dapagliflozin and empagliflozin. METHODS: We searched the PubMed database to identify relevant publications on the mechanism of action of SGLT2 inhibitors and clinical trial reports...
April 24, 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28431476/a-consensus-statement-for-the-clinical-use-of-the-renal-sodium-glucose-co-transporter-2-inhibitor-dapagliflozin-in-patients-with-type-2-diabetes-mellitus
#14
A Avogaro, A Giaccari, P Fioretto, S Genovese, F Purrello, F Giorgino, S Del Prato
The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin ...
April 21, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28426260/the-effects-of-intermittent-use-of-the-sglt-2-inhibitor-dapagliflozin-in-overweight-patients-with-type-2-diabetes-in-japan-a-randomized-crossover-controlled-clinical-trial
#15
Kanako Kato, Kunihiro Suzuki, Chie Aoki, Masaaki Sagara, Takafumi Niitani, Sho Wakamatsu, Kazunori Yanagi, Yoshimasa Aso
BACKGROUND: This study examined the effects of short-term administration of the sodium glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, on visceral fat area (VFA) in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this randomized, crossover, controlled clinical trial, overweight patients with type 2 diabetes were randomized to treatment with 5 mg dapagliflozin for the first (n = 27) or second 12-week study period (n = 29). The parameters evaluated at baseline and after 12 and 24 weeks included blood pressure, hemoglobin A1c (HbA1c), body composition, VFA, and subcutaneous fat area (SFA)...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28418262/adherence-and-persistence-in-patients-with-type-2-diabetes-mellitus-newly-initiating-canagliflozin-dapagliflozin-dpp-4s-or-glp-1s-in-the-united-states
#16
Jennifer Cai, Victoria Divino, Chakkarin Burudpakdee
OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors were first approved in the US in 2013; therefore, real-world (RW) studies describing outcomes are limited. This retrospective study evaluated adherence and persistence among patients initiating canagliflozin (CANA), dapagliflozin (DAPA), GLP-1 agonists (GLP-1s), and DPP-4 inhibitors (DPP-4s) over a 12-month follow-up from a US managed care perspective. METHODS: Patients newly initiating CANA, DAPA, GLP-1s, or DPP-4s from February 1, 2014-June 30, 2014 were identified from the QuintilesIMS PharMetrics Plus Database...
May 8, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28417527/effects-of-dapagliflozin-on-insulin-requirement-glucose-excretion-and-%C3%A3-hydroxybutyrate-levels-are-not-related-to-baseline-hba1c-in-youth-with-type-1-diabetes
#17
Torben Biester, Baerbel Aschemeier, Maryam Fath, Marcel Frey, Markus F Scheerer, Olga Kordonouri, Thomas Danne
Youth with type 1 diabetes (T1D) infrequently achieve HbA1c targets. Therefore, this placebo-controlled, randomized, crossover study was set up to assess the safety, effect and pharmacokinetics of a single dose of 10 mg dapagliflozin (DAPA) as add-on to insulin in relationship to HbA1c in youth. 33 youths (14 males, median age 16 years, diabetes duration 8 years) were included and stratified into three baseline HbA1c categories (<7.5%, 7.5 to 9.0% or >9.0; n = 11 each). During the study period of 24 hours, intravenous insulin administration and glucose-infusion kept blood glucose levels between 160-220 mg/dl...
April 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28412482/dapagliflozin-citric-acid-cocrystal-showing-better-solid-state-properties-than-dapagliflozin
#18
Jun-Hui Deng, Tong-Bu Lu, Changquan Calvin Sun, Jia-Mei Chen
Dapagliflozin (DAP) is a potent and selective sodium-glucose contransporter-2 inhibitor, for treating type 2 diabetes. DAP propanediol monohydrate (DAP-PDO-H2O, 1:1:1) is the solid form used in the current tablet product to address the severe hygroscopicity problem of DAP free form. DAP-PDO-H2O, however, suffers the problem of instability when exposed to high temperature, which renders it amorphous. In this work, we report on the preparation and evaluation of a new 1:1 cocrystal between DAP and citric acid (DAP-CA)...
April 13, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28383856/-dapagliflozin-forxiga%C3%A2-sglt-2-cotransporter-inhibitor-as-glucose-lowering-agent-in-type-2-diabetes
#19
REVIEW
A J Scheen
Dapagliflozin, a specific inhibitor of sodium-glu¬cose cotransporters type 2 (SGLT2, inhibits glucose reabsorp¬tion in renal tubules and thus promotes glucosuria. This effect results in a reduction in fasting and postprandial glycaemia and a decrease of glycated haemoglobin (HbA1c), with a minor risk of hypoglycaemia, a weight reduction and a reduction in arterial blood pressure. The efficacy of empagliflozin on HbA1c reduction increases according to the level of hyper¬glycaemia but decreases in patients with renal insufficiency...
October 2016: Revue Médicale de Liège
https://www.readbyqxmd.com/read/28376855/effects-of-the-sglt2-inhibitor-dapagliflozin-on-hdl-cholesterol-particle-size-and-cholesterol-efflux-capacity-in-patients-with-type-2-diabetes-a-randomized-placebo-controlled-trial
#20
Gian Paolo Fadini, Benedetta Maria Bonora, Giancarlo Zatti, Nicola Vitturi, Elisabetta Iori, Maria Cristina Marescotti, Mattia Albiero, Angelo Avogaro
BACKGROUND: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) reduce glucose levels, body weight, and blood pressure, possibly resulting in cardiovascular protection. In phase III trials, SGLT2i were shown to increase HDL cholesterol. We aimed to evaluate whether the SGLT2i dapagliflozin affects HDL function in a randomized placebo-controlled trial. METHODS: Thirty-three type 2 diabetic patients were randomized to receive dapagliflozin 10 mg or placebo for 12 weeks on top of their glucose lowering medications...
April 4, 2017: Cardiovascular Diabetology
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