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Sodium glucose transport inhibitors

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https://www.readbyqxmd.com/read/29227973/will-canagliflozin-lend-credence-to-the-potential-effects-of-sodium-glucose-co-transporter-2-inhibitors-on-renal-endpoints-in-diabetic-nephropathy
#1
Joshua J Neumiller, Connie M Rhee, Kamyar Kalantar-Zadeh
No abstract text is available yet for this article.
December 11, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/29226041/dapagliflozin-cardiovascular-safety-and-benefits-in-type-2-diabetes-mellitus
#2
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
#3
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
#4
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/29216336/managing-diabetic-kidney-disease
#5
Sagen Zac-Varghese, Peter Winocour
Introduction: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD). This review covers the pillars of care essential for the management of diabetic kidney disease (DKD) including (1) early diagnosis, (2) improved glycaemic control, (3) treatment of hypertension, (4) identification and treatment of associated metabolic bone disease and (5) identification and effective management of dyslipidaemia and additional cardiovascular risk factors. Sources of data: We searched PubMed for articles using search terms: diabetic nephropathy, diabetic kidney disease, diabetes and chronic kidney disease...
December 5, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29213337/effectiveness-of-long-term-treatment-with-sglt2-inhibitors-real-world-evidence-from-a-specialized-diabetes-center
#6
Yotsapon Thewjitcharoen, Nalin Yenseung, Areeya Malidaeng, Soontaree Nakasatien, Phawinpon Chotwanvirat, Sirinate Krittiyawong, Ekgaluck Wanothayaroj, Thep Himathongkam
Background: Diabetes is a progressive disease needing multiple drugs for achieving and maintaining good glycemic control. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a novel class of anti-diabetic agent which offers several beneficial effects. However, the long-term effectiveness in clinical practice and safety data of SGLT2 inhibitors is limited, especially in Asian patients. To better understand the effectiveness of SGLT2i in clinical practice, we conducted a retrospective evaluation of patients with diabetes on SGLT2i...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/29211300/fluorine-directed-glycosylation-enables-the-stereocontrolled-synthesis-of-selective-sglt2-inhibitors-for-type-ii-diabetes
#7
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/29210642/antidiabetics-structural-diversity-of-molecules-with-a-common-aim
#8
Jelena B Popovic-Dordevic, Ivana I Jevtic, Tatjana P Stanojkovic
BACKGROUND: Diabetes mellitus type 2 (DMT2) is an endocrine disease of global proportions which is currently affecting 1 in 12 adults in the world, with still increasing prevalence. World Health Organization (WHO) declared this worldwide health problem, as an epidemic disease, to be the only non-infectious disease with such categorization. People with DMT2 are at increased risk of various complications and have shorter life expectancy. The main classes of oral antidiabetic drugs accessible today for DMT2 vary in their chemical composition, modes of action, safety profiles and tolerability...
December 5, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29206832/the-effects-of-dipeptidyl-peptidase-4-inhibitors-on-bone-fracture-among-patients-with-type-2-diabetes-mellitus-a-network-meta-analysis-of-randomized-controlled-trials
#9
Jun Yang, Chao Huang, Shanshan Wu, Yang Xu, Ting Cai, Sanbao Chai, Zhirong Yang, Feng Sun, Siyan Zhan
AIM: The association between dipeptidyl peptidase-4 inhibitors (DPP-4is), a class of anti-diabetes, and bone fracture in patients with type 2 diabetes mellitus (T2DM) is unknown. This meta-analysis aimed to systematically evaluate the effects of DPP-4is on bone fracture in T2DM patients. METHODS: We searched the Cochrane Library, Embase, Medline and ClinicalTrials.gov from inception through April 28th, 2016 to identify randomized controlled trials (RCTs) that compared DPP-4is with placebo or other anti-diabetes in T2DM patients...
2017: PloS One
https://www.readbyqxmd.com/read/29202593/ipragliflozin-and-sodium-glucose-transporter-2-inhibitors-to-reduce-liver-fat-will-the-prize-we-sought-be-won
#10
Kalliopi Pafili, Efstratios Maltezos, Nikolaos Papanas
No abstract text is available yet for this article.
December 5, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/29196150/sglt2-inhibitors-with-cardiovascular-benefits-transforming-clinical-care-in-type2-diabetes-mellitus
#11
REVIEW
Michael d'Emden, John Amerena, Gary Deed, Carol Pollock, Mark E Cooper
Cardiovascular risk reduction in individuals with Type 2 diabetes mellitus (T2DM) is a key part of clinical management. Sodium-glucose co-transporter (SGLT2) inhibitors improve glycaemic control, reduce body weight and decrease blood pressure. In addition, the SGLT2 inhibitors empagliflozin and canagliflozin reduced the risk of composite cardiovascular events in high-risk individuals with T2DM in the EMPA-REG OUTCOME trial and the CANVAS Program, respectively. Empagliflozin also reduced cardiovascular deaths and improved renal outcomes...
November 28, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/29193543/initiation-of-dapagliflozin-and-treatment-emergent-fractures
#12
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/29185199/predictors-for-the-treatment-effect-of-sodium-glucose-co-transporter-2-inhibitors-in-patients-with-type-2-diabetes-mellitus
#13
Shusuke Yagi, Ken-Ichi Aihara, Takeshi Kondo, Kiyoe Kurahashi, Sumiko Yoshida, Itsuro Endo, Daiju Fukuda, Yutaka Nakaya, Kin-Ichiro Suwaki, Takashi Takeji, Toshihiro Wada, Hotimah Masdan Salim, Saori Hama, Tomomi Matsuura, Takayuki Ise, Kenya Kusunose, Koji Yamaguchi, Takeshi Tobiume, Hirotsugu Yamada, Takeshi Soeki, Tetsuzo Wakatsuki, Munehide Matsuhisa, Michio Shimabukuro, Masashi Akaike, Masataka Sata
INTRODUCTION: Predictors for the effect of sodium glucose co-transporter 2 (SGLT2) inhibitors at lowering hemoglobin A1c (HbA1c) levels in type 2 diabetes mellitus patients remain unclear. We therefore aimed to elucidate these predictors in type 2 diabetes patients after 3 months of SGLT2 treatment. METHODS: A total of 302 consecutive type 2 diabetes patients who had been treated with SGLT2 inhibitors as monotherapy or add-on therapy to existing antidiabetic treatments were enrolled retrospectively...
November 28, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29177922/sglt1-and-sglt1-inhibitors-a-role-to-be-assessed-in-the-current-clinical-practice
#14
Leonardo Spatola, Silvia Finazzi, Claudio Angelini, Marco Dauriz, Salvatore Badalamenti
Diabetes is a complex disease of increasingly common occurrence worldwide. Attaining optimal glycemic control is the main challenge to prevent the development of diabetes-related complications and/or to stop their progression. In recent years, the pharmacologic toolkit for the treatment of diabetes has considerably expanded, thus paving the way to more pathophysiology-oriented therapies. For instance, the sodium-glucose cotransporters SGLT2 and SGLT1 have been in the spotlight because of better knowledge of their physiology and therapeutic potential...
November 24, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29174026/adverse-events-with-sodium-glucose-co-transporter-2-inhibitors-a%C3%A2-global-analysis-of-international-spontaneous-reporting-systems
#15
E Raschi, M Parisotto, E Forcesi, M La Placa, G Marchesini, F De Ponti, E Poluzzi
BACKGROUND AND AIMS: We assessed post-marketing safety of sodium-glucose co-transporter-2 inhibitors (SGLT2-Is) by analyzing adverse events (AEs) reported in international pharmacovigilance databases. METHODS AND RESULTS: Eudravigilance, WHO-Vigibase (as of Feb 25, 2017) and the FDA Adverse Event Reporting System (FAERS, from 2004 to 2016 second quarter) were queried to extract AEs recording SGLT2-Is as suspect. Disproportionality analyses (case/non-case method) were performed in FAERS by calculating the reporting odds ratios (RORs) from System Organ Classes (SOCs) to Preferred Terms (PTs) (precise clinical entities)...
October 18, 2017: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/29168387/impacts-of-sodium-glucose-co-transporter-type-2-inhibitors-on-central-blood-pressure
#16
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
#17
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/29157798/euglycemic-diabetic-ketoacidosis-secondary-to-dapagliflozin-use-a-case-report
#18
Felicity Brown, Tamara McColl
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are a novel class of oral antihyperglycemic agents. They are associated with rare cases of euglycemic diabetic ketoacidosis (DKA), which presents a diagnostic challenge in the emergency department (ED) and potentially severe consequences if missed. CASE REPORT: A 53-year-old man with type 2 diabetes mellitus and a recent Roux-en-Y gastric bypass surgery presented to the ED with nausea, vomiting, and generalized abdominal pain...
November 17, 2017: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/29157245/low-1-5-anhydroglucitol-levels-are-associated-with-long-term-cardiac-mortality-in-acute-coronary-syndrome-patients-with-hemoglobin-a1c-levels-less-than-7-0
#19
Shohei Ouchi, Kazunori Shimada, Tetsuro Miyazaki, Shuhei Takahashi, Yurina Sugita, Megumi Shimizu, Azusa Murata, Tomoyasu Kadoguchi, Takao Kato, Tatsuro Aikawa, Shoko Suda, Eiryu Sai, Masaru Hiki, Hiroshi Iwata, Takatoshi Kasai, Katsumi Miyauchi, Hiroyuki Daida
BACKGROUND: Diabetes mellitus is considered an important risk factor for cardiovascular diseases. High hemoglobin A1c (HbA1c) levels, which indicate poor glycemic control, have been associated with occurrence of cardiovascular diseases. There are few parameters which can predict cardiovascular risk in patients with well-controlled diabetes. Low 1,5-anhydroglucitol (1,5-AG) levels are considered a clinical marker of postprandial hyperglycemia. We hypothesized that low 1,5-AG levels could predict long-term mortality in acute coronary syndrome (ACS) patients with relatively low HbA1c levels...
November 21, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29145743/novel-avenues-for-drug-discovery-in-diabetic-kidney-disease
#20
Matthew D Breyer, Matthias Kretzler
Diabetic kidney disease (DKD) has emerged as major cause of morbidity and mortality. After progressing to renal failure, over 70% of DKD patients are dead with five years. New treatments to slow this progression are desperately needed. Areas covered: This review highlights the current treatment options for people with DKD with a particular focus on angiotensin pathway blockade and the potential use of sodium glucose linked transporter 2 (SGLT2) inhibitors. These treatments are associated with an initial decrease in glomerular filtration rate (GFR) and albuminuria; there is also attention on renal hyperfiltration as therapeutic target...
November 16, 2017: Expert Opinion on Drug Discovery
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