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Dapagliflozin

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https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#1
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29322605/declare-timi-58-participants-baseline-characteristics
#2
Itamar Raz, Ofri Mosenzon, Marc P Bonaca, Avivit Cahn, Eri T Kato, Michael G Silverman, Deepak L Bhatt, Lawrence A Leiter, Darren K McGuire, John Wilding, Ingrid Am Gause-Nilsson, Anna Maria Langkilde, Peter A Johansson, Marc S Sabatine, Stephen D Wiviott
BACKGROUND: Cardiovascular (CV) outcome trials with new glucose lowering agents (GLA) are designed to prove CV safety in high CV risk populations. However, the level of CV risk differs greatly among trials, which may influence comparability and generalizability of results. AIM: We describe baseline characteristics of participants randomized in the Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58) trial, the pivotal study to assess CV outcomes with dapagliflozin...
January 11, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29322486/dapagliflozin-and-empagliflozin-ameliorate-hepatic-dysfunction-among-chinese-subjects-with-diabetes-in-part-through-glycemic-improvement-a-single-center-retrospective-observational-study
#3
Paul Chi Ho Lee, Yunjuan Gu, Man Yi Yeung, Carol Ho Yi Fong, Yu Cho Woo, Wing Sun Chow, Kathryn Tan, Karen Siu Ling Lam
INTRODUCTION: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve hepatic dysfunction, although studies focusing on their underlying mechanisms are lacking, especially ones on dapagliflozin and empagliflozin. Here, we investigated the relationship between amelioration of hepatic dysfunction and improvement in various metabolic parameters among Chinese subjects with type 2 diabetes (T2DM). METHODS: This was a single-center, retrospective, observational study that involved 115 Chinese participants with T2DM treated with either dapagliflozin or empagliflozin for at least 6 months between July 2016 and February 2017...
January 10, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29316164/effects-of-exenatide-once-weekly-plus-dapagliflozin-exenatide-once-weekly-or-dapagliflozin-added-to-metformin-monotherapy-on-body-weight-systolic-blood-pressure-and-triglycerides-in-patients-with-type-2-diabetes-in-the-duration-8-study
#4
Serge A Jabbour, Juan P Frías, Cristian Guja, Elise Hardy, Azazuddin Ahmed, Peter Öhman
This post hoc analysis assessed the effects on cardiovascular risk factors of body weight, systolic blood pressure (SBP), and triglycerides after 28 weeks' treatment with exenatide once weekly (QW) plus dapagliflozin, as compared with exenatide QW or dapagliflozin, in patient subpopulations from the DURATION-8 trial of patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin alone. Subgroups of patients were stratified according to their baseline body weight, SBP, and triglycerides...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29316157/dapagliflozin-for-prednisone-induced-hyperglycemia-in-acute-exacerbation-of-chronic-obstructive-pulmonary-disease
#5
Maaike C Gerards, Gerdien E Venema, Kornelis W Patberg, Martijn Kross, Bert Jan Potter van Loon, Ilse M G Hageman, Dominic Snijders, Dees P M Brandjes, Joost B L Hoekstra, Titia M Vriesendorp, Victor E A Gerdes
This study aimed to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in subjects with prednisone-induced hyperglycemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicenter double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared to placebo. Glycemic control and incidence of hypoglycemia were measured through a blinded subcutaneous continuous glucose measurement device...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29301520/sglt-2-inhibition-with-dapagliflozin-reduces-tissue-sodium-content-a-randomised-controlled-trial
#6
M V Karg, A Bosch, D Kannenkeril, K Striepe, C Ott, M P Schneider, F Boemke-Zelch, P Linz, A M Nagel, J Titze, M Uder, R E Schmieder
BACKGROUND AND AIMS: Sodium tissue content by 23Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes characterized by sodium retention leads to decreased tissue sodium content due to its pharmacological action. MATERIALS AND METHODS: In a prospective double blind, placebo controlled, cross-over trial 59 patients (61 ± 7...
January 4, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29301516/the-effect-of-dapagliflozin-treatment-on-epicardial-adipose-tissue-volume
#7
Takao Sato, Yoshifusa Aizawa, Sho Yuasa, Shohei Kishi, Koichi Fuse, Satoshi Fujita, Yoshio Ikeda, Hitoshi Kitazawa, Minoru Takahashi, Masahito Sato, Masaaki Okabe
BACKGROUND: Glycosuria produced by sodium-glucose co-transporter-2 (SGLT-2) inhibitors is associated with weight loss. SGLT-2 inhibitors reportedly might reduce the occurrence of cardiovascular events. Epicardial adipose tissue (EAT) is a pathogenic fat depot that may be associated with coronary atherosclerosis. The present study evaluated the relationship between an SGLT-2 inhibitor (dapagliflozin) and EAT volume. METHODS: In 40 diabetes mellitus patients with coronary artery disease (10 women and 30 men; mean age of all 40 patients was 67...
January 4, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29301371/the-sodium-glucose-cotransporter-2-inhibitor-dapagliflozin-prevents-renal-and-liver-disease-in-western-diet-induced-obesity-mice
#8
Dong Wang, Yuhuan Luo, Xiaoxin Wang, David J Orlicky, Komuraiah Myakala, Pengyuan Yang, Moshe Levi
Obesity and obesity related kidney and liver disease have become more prevalent over the past few decades, especially in the western world. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic agents with promising effects on cardiovascular and renal function. Given SGLT2 inhibitors exert both anti-diabetic and anti-obesity effects by promoting urinary excretion of glucose and subsequent caloric loss, we investigated the effect of the highly selective renal SGLT2 inhibitor dapagliflozin in mice with Western diet (WD) induced obesity...
January 3, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29285458/sodium-glucose-cotransporter-2-inhibitors-moving-beyond-the-glycemic-treatment-goal
#9
REVIEW
Vishal Gupta, William Canovatchel, B N Lokesh, Ravi Santani, Nishant Garodia
Revelations of the multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) that extend beyond the role of insulin and glucose utilization have been crucial in redefining the treatment paradigm. The focus of treatment is currently directed towards achieving wide-ranging targets encompassing the management of cardiovascular comorbidities that have been evidenced as indispensable aspects of T2DM. While most currently prescribed antihyperglycemic agents have little or no effect on reducing cardiovascular risks, some have been associated with undesirable effects on common risk factors such as weight gain and cardiovascular sequelae...
November 2017: Indian Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29241389/euglycemic-diabetic-ketoacidosis-associated-with-sodium-glucose-cotransporter-type-2-inhibitors-in-patients-with-type-2-diabetes-mellitus-receiving-oral-therapy
#10
Ryan B Dull, Mikayla L Spangler, Emily L Knezevich, Britney M Lau
INTRODUCTION AND OBJECTIVE: Postmarketing reports and warnings of serious adverse events such as diabetic ketoacidosis (DKA) have raised concern regarding the safety of sodium-glucose cotransporter 2 inhibitors (SGLT2i). This report describes 2 cases of symptomatic SGLT2i-associated euglycemic DKA (euDKA) leading to hospitalization in patients with type 2 diabetes mellitus (DM) previously well controlled on oral medications. CASE REPORTS: Subject 1 is a 55-year-old female admitted with euDKA precipitated by infection and managed with intravenous insulin...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/29226041/dapagliflozin-cardiovascular-safety-and-benefits-in-type-2-diabetes-mellitus
#11
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/29225209/dapagliflozin-reduces-fat-mass-without-affecting-muscle-mass-in-type-2-diabetes
#12
Seigo Sugiyama, Hideaki Jinnouchi, Noboru Kurinami, Kunio Hieshima, Akira Yoshida, Katsunori Jinnouchi, Hiroyuki Nishimura, Tomoko Suzuki, Fumio Miyamoto, Keizo Kajiwara, Tomio Jinnouchi
AIM: Sodium-glucose co-transporter 2 inhibitor (SGLT2i) therapy has been demonstrated to improve glycemic control and reduce body weight and fat mass in type 2 diabetes mellitus (T2DM). Here, our aim was to investigate the effects of SGLT2i dapagliflozin-treatment on body muscle mass and muscle fat content in patients with T2DM. METHODS: We prospectively recruited uncontrolled (hemoglobin A1c [HbA1c] >7%) Japanese T2DM patients who had a body mass index (BMI) <35 kg/m2...
December 8, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29216560/identification-of-an-oxime-containing-c-glucosylarene-as-a-potential-inhibitor-of-sodium-dependent-glucose-co-transporter-2
#13
Mao-Chia Yuan, Teng-Kuang Yeh, Chiung-Tong Chen, Jen-Shin Song, Yu-Chen Huang, Tsung-Chih Hsieh, Chung-Yu Huang, Yu-Ling Huang, Min-Hsien Wang, Szu-Huei Wu, Chun-Hsu Yao, Yu-Sheng Chao, Jinq-Chyi Lee
Treatment of hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management. In this study, twenty-seven aryl C-glycosides bearing a C=N/C-N linkage at the glucosyl C6 position were designed, synthesized and evaluated for their inhibitory activity against human SGLT2 (hSGLT2). Compounds with good hSGLT2 inhibition were further investigated to determine their selectivity over hSGLT1. Of these, five representative aryl C-glycosides were chosen for pharmacokinetic analysis...
November 10, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29215189/dapagliflozin-as-add-on-therapy-in-asian-patients-with-type-2-diabetes-inadequately-controlled-on-insulin-%C3%A2-oral-antihyperglycemic-drugs-a-randomized-controlled-trial
#14
Wenying Yang, Jianhua Ma, Yiming Li, Yanbing Li, Zhiguang Zhou, Jae Hyeon Kim, June Zhao, Agata Ptaszynska
BACKGROUND: This 24-week, phase 3, double-blind, placebo-controlled study (NCT02096705) assessed the safety and efficacy of dapagliflozin as add-on to insulin ± oral antihyperglycemic drugs (OADs) in Asian patients with inadequately controlled type 2 diabetes. METHODS: Patients (adults; HbA1c ≥7.5-≤10.5%; body mass index ≤45 kg/m2 ; insulin dose ≥20 IU daily) were randomized to dapagliflozin 10 mg (N=139) or placebo (N=133) to assess the 24-week change in HbA1c (primary outcome), fasting plasma glucose (FPG), body weight, total daily dose of insulin (TDDI), and seated systolic blood pressure (SeSBP; exploratory outcome)...
December 7, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/29211300/fluorine-directed-glycosylation-enables-the-stereocontrolled-synthesis-of-selective-sglt2-inhibitors-for-type-ii-diabetes
#15
Anna Sadurní, Gerald Kehr, Marie Ahlqvist, Helena Peilot Sjögren, Cecilia Kankkonen, Laurent Knerr, Ryan Gilmour
Inhibition of the sodium-glucose co-transporters (SGLT1 and SGLT2) is a validated strategy to address the increasing prevalence of type II diabetes mellitus. However, achieving selective inhibition of human SGLT1 or SGLT2 remains challenging. Orally available small molecule drugs based on the D-glucose core of the natural product Gliflozin have proven to be clinically effective in this regard, effectively impeding glucose reabsorption. Herein, we disclose the influence of molecular editing with fluorine at the C2 position of the pyranose ring of Phlorizin analogues Remogliflozin Etabonate and Dapagliflozin (Farxiga®) to concurrently direct β-selective glycosylation, as is required for biological efficacy, and enhance aspects of the physicochemical profile...
December 6, 2017: Chemistry: a European Journal
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
#16
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/29193543/initiation-of-dapagliflozin-and-treatment-emergent-fractures
#17
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
#18
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/29176433/drug-updates-and-approvals-2017-in-review
#19
Geoffrey Mospan, Cortney Mospan, Shayna Vance, Alyssa Bradshaw, Kalyn Meosky, Kirklin Bowles
In 2017, the FDA approved several new drugs for use in primary care. This article highlights the following new drugs: brodalumab (Siliq), dapagliflozin and saxagliptin (Qtern), dupilumab (Dupixent), oxymetazoline (Rhofade), safinamide (Xadago), and sarilumab (Kevzara).
December 15, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/29174031/acute-renal-failure-with-sodium-glucose-cotransporter-2-inhibitors-analysis-of-the-fda-adverse-event-report-system-database
#20
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
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