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Dapagliflozine

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https://www.readbyqxmd.com/read/28192604/dapagliflozin-lowered-blood-glucose-reduces-respiratory-p-aeruginosa-infection-in-diabetic-mice
#1
Annika Åstrand, Cecilia Wingren, Audra Benjamin, John S Tregoning, James P Garnett, Helen Groves, Simren Gill, Maria Orogo-Wenn, Anders J Lundqvist, Dafydd Walters, David M Smith, John D Taylor, Emma H Baker, Deborah L Baines
BACKGROUND AND PURPOSE: Hyperglycaemia increases glucose concentrations in airway surface liquid (ASL) and increases the risk of pulmonary Pseudomonas aeruginosa infection. We determined whether reduction of blood and airway glucose concentrations by the anti-diabetic drug dapagliflozin could reduce P. aeruginosa growth/survival in the lungs of diabetic mice. EXPERIMENTAL APPROACH: The effect of dapagliflozin on blood and airway glucose concentration, the inflammatory response and infection were investigated in C57BL/6 J (wild type, WT) or db/db (leptin receptor-deficient) mice, treated orally with dapagliflozin prior to intranasal dosing with lipopolysaccharide (LPS) or inoculation with P...
February 13, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28176222/saxagliptin-dapagliflozin-a-review-in-type-2-diabetes-mellitus
#2
Karly P Garnock-Jones
Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern(®)) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin + dapagliflozin. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of saxagliptin/dapagliflozin in this indication...
February 7, 2017: Drugs
https://www.readbyqxmd.com/read/28144158/following-the-results-of-the-empa-reg-outcome-trial-with-empagliflozin-is-it-possible-to-speak-of-a-class-effect
#3
Francisco Javier Ampudia-Blasco, Irene Romera, Bernat Ariño, Ramón Gomis
BACKGROUND: The recently published cardiovascular outcomes data for the first sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, have shown cardiovascular safety and additional benefits in patients with type 2 diabetes and established cardiovascular disease. Empagliflozin showed lower rates of death from cardiovascular causes or from any causes and lower hospitalization rates from heart failure compared with placebo, both in addition to standard care. This commentary discusses the existence of a possible class effect considering the available evidence described for other SGLT2 inhibitors...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/28132924/dapagliflozin-a-selective-sglt2-inhibitor-attenuated-cardiac-fibrosis-by-regulating-the-macrophage-polarization-via-stat3-signaling-in-infarcted-rat-hearts
#4
Tsung-Ming Lee, Nen-Chung Chang, Shinn-Zong Lin
During myocardial infarction, infiltrated macrophages have pivotal roles in cardiac remodeling and delayed M1 toward M2 macrophage phenotype transition is considered one of the major factors for adverse ventricular remodeling. We investigated whether dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, attenuates cardiac fibrosis via regulating macrophage phenotype by a reactive oxygen and nitrogen species (RONS)/STAT3-dependent pathway in postinfarcted rats. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline, dapagliflozin (a specific SGLT2 inhibitor), phlorizin (a nonspecific SGLT1/2 inhibitor), dapagliflozin + S3I-201 (a STAT3 inhibitor), or phlorizin + S3I-201 for 4 weeks...
January 26, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28132008/compensatory-changes-in-energy-balance-during-dapagliflozin-treatment-in-type-2-diabetes-mellitus-a-randomised-double-blind-placebo-controlled-cross-over-trial-energize-study-protocol
#5
Surya Panicker Rajeev, Victoria S Sprung, Carl Roberts, Jo A Harrold, Jason C G Halford, Andrej Stancak, Emma J Boyland, Graham J Kemp, Daniel J Cuthbertson, John P H Wilding
INTRODUCTION: Sodium glucose cotransporter 2 (SGLT2) inhibitors are effective blood-glucose-lowering medications with beneficial effects on body weight in patients with type 2 diabetes mellitus (T2DM). However, observed weight loss is less than that predicted from quantified glycosuria, suggesting a compensatory increase in energy intake or a decrease in energy expenditure. Studies using dual-energy X-ray absorptiometry (DEXA) have suggested most body weight change is due to loss of adipose tissue, but organ-specific changes in fat content (eg, liver, skeletal muscle) have not been determined...
January 27, 2017: BMJ Open
https://www.readbyqxmd.com/read/28131071/early-drug-use-of-dapagliflozin-prescribed-by-general-practitioners-and-diabetologists-in-germany
#6
Matthew Hankins, Katherine Tsai, Joseph Kim, Niklas Hammar
OBJECTIVES: Dapagliflozin is an inhibitor of the human sodium-glucose co-transporter 2 (SGLT2) that has been shown to improve glycaemic control in patients with type 2 diabetes mellitus (T2DM). This study aimed to evaluate the characteristics and treatment patterns of dapagliflozin users in comparison to users of other anti-diabetic (AD) treatments in Germany. METHODS: Data from patients with T2DM initiating at least one prescription for dapagliflozin or other AD therapy between November 2012 and April 2014 were collected from the IMS German Disease Analyzer database...
November 9, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28116795/novel-oral-glucose-lowering-drugs-compared-to-insulin-are-associated-with-lower-risk-of-all-cause-mortality-cardiovascular-events-and-severe-hypoglycemia-in-type-2-diabetes-patients
#7
Thomas Nyström, Johan Bodegard, David Nathanson, Marcus Thuresson, Anna Norhammar, Jan W Eriksson
AIMS: To investigate the association of novel oral glucose lowering drugs (GLDs) compared with insulin to risk of all-cause mortality, cardiovascular disease (CVD) and severe hypoglycaemia. METHODS: During 2013-2014 all type 2 diabetes patients in Sweden identified as new users of novel oral GLDs, i.e. either dipeptidyl-peptidase-4 inhibitors (DPP-4i) or sodium glucose cotransporter-2 inhibitors (SGLT-2i; only dapagliflozin available in Sweden during the study period), compared to insulin treatment in the Prescribed Drug Register were included and followed in the Patient- and Cause of Death Registers...
January 24, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28116093/inhibition-of-sglt2-alleviates-diabetic-nephropathy-by-suppressing-high-glucose-induced-oxidative-stress-in-type-1-diabetic-mice
#8
Takashi Hatanaka, Daisuke Ogawa, Hiromi Tachibana, Jun Eguchi, Tatsuyuki Inoue, Hiroshi Yamada, Kohji Takei, Hirofumi Makino, Jun Wada
It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28105986/canagliflozin-dapagliflozin-and-empagliflozin-monotherapy-for-treating-type-2-diabetes-systematic-review-and-economic-evaluation
#9
Rhona Johnston, Olalekan Uthman, Ewen Cummins, Christine Clar, Pamela Royle, Jill Colquitt, Bee Kang Tan, Andrew Clegg, Saran Shantikumar, Rachel Court, J Paul O'Hare, David McGrane, Tim Holt, Norman Waugh
BACKGROUND: Most people with type 2 diabetes are overweight, so initial treatment is aimed at reducing weight and increasing physical activity. Even modest weight loss can improve control of blood glucose. If drug treatment is necessary, the drug of first choice is metformin. However, some people cannot tolerate metformin, which causes diarrhoea in about 10%, and it cannot be used in people with renal impairment. This review appraises three of the newest class of drugs for monotherapy when metformin cannot be used, the sodium-glucose co-transporter 2 (SGLT2) inhibitors...
January 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28102030/impact-of-sodium-glucose-cotransporter-2-inhibitors-on-nonglycemic-outcomes-in-patients-with-type-2-diabetes
#10
Jennifer M Trujillo, Wesley A Nuffer
The efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitors canagliflozin, dapagliflozin, and empagliflozin in reducing hyperglycemia in patients with type 2 diabetes is well documented. In addition, positive effects have been observed with these agents on nonglycemic variables, such as reductions in body weight and blood pressure, which may confer additional health benefits. SGLT2 inhibitors are also associated with evidence of renal-protecting benefits. Furthermore, during the landmark Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, a substantial reduction in major adverse cardiovascular outcomes was demonstrated with empagliflozin therapy...
January 19, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28098426/dapagliflozin-in-patients-with-type-1-diabetes-a-post-hoc-analysis-of-the-effect-of-insulin-dose-adjustments-on-24-hour-continuously-monitored-mean-glucose-and-fasting-beta-hydroxybutyrate-levels-from-a-phase-iia-pilot-study
#11
Robert R Henry, Paresh Dandona, Jeremy Pettus, Sunder Mudaliar, John Xu, Lars Hansen
AIMS: To investigate the effects of total daily insulin dose (TDD) reductions on 24-hour continuously monitored mean glucose and fasting beta-hydroxybutyrate (a marker for diabetic ketosis/ketoacidosis [DKA]) using patient-level data from a 14-day, pilot study of dapagliflozin in type 1 diabetes. MATERIALS AND METHODS: Exploratory correlation analysis was performed post-hoc to determine the relationship between change in TDD and a) 24-hour mean glucose (by continuous glucose monitoring) and b) fasting beta-hydroxybutyrate, in 70 patients with type 1 diabetes receiving insulin and dapagliflozin (1-, 2...
January 18, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28097882/antidiabetic-agents-and-cardiovascular-outcomes-in-patients-with-heart-diseases
#12
Judy W M Cheng, Hisham A Badreldin, Dhiren K Patel, Snehal H Bhatt
This article reviews evidence of benefits and risk of antidiabetic agents in cardiovascular (CV) outcomes, with a focus on medications approved by the FDA since 2008. Peer-reviewed articles were identified from MEDLINE and Current Content database (both 1966 to October 1, 2016) using the search terms insulin, metformin, rosiglitazone, pioglitazone, glyburide, glipizide, glimepiride, acarbose, miglitol, albiglutide, exenatide, liraglutide, lixisenatide, dulaglutide, pramlintide, meglitinide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, colesevalam, bromocriptine, mortality, myocardial infarction (MI), heart failure, (HF) and stroke...
January 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#13
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28086872/dapagliflozin-decreases-small-dense-low-density-lipoprotein-cholesterol-and-increases-high-density-lipoprotein-2-cholesterol-in-patients-with-type-2-diabetes-comparison-with-sitagliptin
#14
Toshiyuki Hayashi, Tomoyasu Fukui, Noriko Nakanishi, Saki Yamamoto, Masako Tomoyasu, Anna Osamura, Makoto Ohara, Takeshi Yamamoto, Yasuki Ito, Tsutomu Hirano
BACKGROUND: The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies. METHODS: This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28077257/real-world-effectiveness-and-safety-of-dapagliflozin-therapy-added-to-a-glp1-receptor-agonist-in-patients-with-type-2-diabetes
#15
J J Gorgojo-Martínez, C Serrano-Moreno, A Sanz-Velasco, G Feo-Ortega, F Almodóvar-Ruiz
BACKGROUND AND AIM: To evaluate the effectiveness and safety of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, dapagliflozin, in patients with type 2 diabetes mellitus (T2DM) and background glucagon-like peptide-1 receptor agonist (GLP1-RA) therapy. METHODS AND RESULTS: This is a 12-month, real-world observational study, which assessed the effectiveness and safety of dapagliflozin in patients with T2DM and background GLP1-RA therapy. The main outcome measures were changes in A1C and weight at 6 and 12 months from baseline...
November 23, 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/28068585/effects-of-phosphate-binders-on-the-gastrointestinal-absorption-of-arsenate-and-of-an-sglt2-inhibitor-drug-on-the-urinary-excretion-of-arsenite-in-mice
#16
Miklós Poór, Balázs Németi, Zoltán Gregus
Arsenate (As(V)) and arsenite (As(III)) are typical sources of acute and chronic arsenic poisoning. Therefore, reducing inner exposure to these arsenicals is a rational objective. Because As(V) mimics phosphate, phosphate binder drugs may decrease the intestinal As(V) absorption. Indeed, lanthanum and aluminium salts and sevelamer removed As(V) from solution in vitro, especially at acidic pH. In mice gavaged with As(V), lanthanum chloride, lanthanum carbonate and aluminium hydroxide given orally also lowered the urinary excretion and tissue levels of As(V) and its metabolites, indicating that they decreased the gastrointestinal As(V) absorption...
January 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28052965/the-sglt2-inhibitor-dapagliflozin-prevents-cardiomyopathy-in-a-diabetic-lipodystrophic-mouse-model
#17
Michael Joubert, Benoît Jagu, David Montaigne, Xavier Marechal, Angela Tesse, Audrey Ayer, Lucile Dollet, Cédric Le May, Gilles Toumaniantz, Alain Manrique, Flavien Charpentier, Bart Staels, Jocelyne Magré, Bertand Cariou, Xavier Prieur
Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). T2DM is associated with altered cardiac energy metabolism, leading to ectopic lipid accumulation and glucose overload, the exact contribution of these two parameters remaining unclear. To provide new insight into the mechanism driving the development of diabetic cardiomyopathy, we studied a unique model of T2DM: lipodystrophic Bscl2(-/-) (seipin knockout (SKO)) mice. Echocardiography and cardiac magnetic resonance imaging revealed hypertrophic cardiomyopathy with left ventricular dysfunction in SKO mice and these two abnormalities were strongly correlated with hyperglycemia...
January 4, 2017: Diabetes
https://www.readbyqxmd.com/read/28039605/pharmacokinetic-characteristics-and-clinical-efficacy-of-an-sglt2-inhibitor-plus-dpp-4-inhibitor-combination-therapy-in-type-2-diabetes
#18
REVIEW
André J Scheen
Type 2 diabetes (T2D) generally requires a combination of several pharmacological approaches to control hyperglycaemia. Combining a sodium-glucose cotransporter type 2 inhibitor (SGLT2I, also known as gliflozin) and a dipeptidyl peptidase-4 inhibitor (DPP-4I, also known as gliptin) appears to be an attractive strategy because of complementary modes of action. This narrative review analyzes the pharmacokinetics and clinical efficacy of different combined therapies with an SGLT2I (canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, ipragliflozin, luseogliflozin, tofogliflozin) and DPP-4I (linagliptin, saxagliptin, sitagliptin, teneligliptin)...
December 30, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28008402/dapagliflozin-induced-acute-on-chronic-liver-injury
#19
Joshua A Levine, Amy Ann Lo, Amisha Wallia, Melinda Rogers, Lisa B VanWagner
Sodium-glucose cotransporter 2 inhibitors are a new class of oral hypoglycemic agents, and thus safety data are limited. We present a 48-year-old woman with type 2 diabetes mellitus and Child's Class A cirrhosis secondary to nonalcoholic steatohepatitis presenting with jaundice and acute cholestatic liver injury. Other than starting dapagliflozin, she reported no medication changes or supplement use. Before treatment, her total bilirubin was 1.2 mg/dL. On admission, her liver values were elevated and liver biopsy was consistent with drug-induced liver injury...
August 2016: ACG Case Reports Journal
https://www.readbyqxmd.com/read/28001016/effect-of-dapagliflozin-administration-on-metabolic-syndrome-insulin-sensitivity-and-insulin-secretion
#20
Manuel González-Ortiz, Miriam Méndez-Del Villar, Esperanza Martínez-Abundis, Alejandra M Ramírez-Rodríguez
AIM: To evaluate the effect of dapagliflozin on metabolic syndrome (MetS), insulin sensitivity and insulin secretion. METHODS: A randomized, double blind, placebo-controlled clinical trial was carried out in 24 patients with MetS. Glucose and insulin levels were measured every 30 min for 2-h after a 75-g dextrose load. Metabolic profile was also evaluated before and after the pharmacological intervention. Twelve patients received dapagliflozin (10 mg) before breakfast for 90 days...
December 20, 2016: Minerva Endocrinologica
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