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Sodium glucose transport inhibitors

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https://www.readbyqxmd.com/read/29440005/interaction-between-the-sodium-glucose-linked-transporter-2-inhibitor-dapagliflozin-and-the-loop-diuretic-bumetanide-in-normal-human-subjects
#1
Christopher S Wilcox, Wen Shen, David W Boulton, Bruce R Leslie, Steven C Griffen
BACKGROUND: Dapagliflozin inhibits the sodium-glucose-linked transporter 2 in the renal proximal tubule, thereby promoting glycosuria to reduce hyperglycemia in type 2 diabetes mellitus. Because these patients may require loop diuretics, and sodium-glucose-linked transporter 2 inhibition causes an osmotic diuresis, we evaluated the diuretic interaction between dapagliflozin and bumetanide. METHODS AND RESULTS: Healthy subjects (n=42) receiving a fixed diet with ≈110 mmol·d -1 of Na + were randomized to bumetanide (1 mg·d -1 ), dapagliflozin (10 mg·d -1 ), or both for 7 days, followed by 7 days of both...
February 10, 2018: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29430814/sglt-2-inhibitors-and-the-risk-of-lower-limb-amputation-is-this-a-class-effect
#2
Charles Khouri, Jean-Luc Cracowski, Matthieu Roustit
OBJECTIVE: Inhibitors of the sodium-glucose co-transporter-2 (SGLT-2) are a novel class of glucose lowering agents showing promising results. However, the use of canagliflozin has been associated with an increased risk of lower-limb amputation. Whether this risk concerns other SGLT-2 inhibitors is unclear. METHODS: We performed a disproportionality analysis using the WHO global database of individual case safety reports (VigiBase®) to address this issue. RESULTS: Among the 8,293,886 reports available between January 2013 and December 2017, we identified 79 reports of lower-limb amputations associated with SGLT-2 inhibitors...
February 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29429476/-diagnosis-and-treatment-of-maturity-onset-diabetes-of-the-young-type-3
#3
Kathrine Rose, Alexander Sidelmann Christensen, Heidi Storgaard, Sofie Hædersdal, Torben Hansen, Filip Krag Knop, Tina Vilsbøll
Maturity onset diabetes of the young type 3 (MODY3) is the most prevalent type of monogenetic diabetes. Treatment guidelines differ from both Type 1 diabetes and Type 2 diabetes. First-line treatment is a long-acting sulphonylurea, which lowers the plasma glucose level effectively, however with the risk of hypoglycaemia. When hypoglycaemia is a problem, short-acting sulphonylureas, glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors may be used as alternatives. Metformin, glitazones and sodium glucose transporter 2-inhibitors have only limited applicability in MODY3...
February 5, 2018: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/29424089/cardiovascular-benefits-of-sglt2-inhibition-in-diabetes-and-chronic-kidney-diseases
#4
EDITORIAL
Anita T Layton, Volker Vallon
In addition to being a leading cause of end-stage renal disease, diabetes mellitus is also associated with an elevated risk of heart failure. A new class of anti-hyperglycaemic drugs are the sodium-glucose cotransporter 2 (SGLT2) inhibitors, which attenuate postprandial increases in blood glucose by targeting its reabsorption along the early proximal tubule and enhancing urinary glucose excretion. Because the transport of glucose and Na+ in the proximal tubule is coupled, inhibition of SGLT2 also reduces proximal tubular Na+ and fluid reabsorption, and induces natriuresis and diuresis...
February 8, 2018: Acta Physiologica
https://www.readbyqxmd.com/read/29416209/effects-on-glycemic-control-in-impaired-wound-healing-in-spontaneously-diabetic-torii-sdt-fatty-rats
#5
Miyajima Katsuhiro, Soon Hui Teoh, Hideaki Yamashiro, Masami Shinohara, Fatchiyah Fatchiyah, Takeshi Ohta, Takahisa Yamada
Introduction: Impaired diabetic wound healing is an important issue in diabetic complications. The present study aims to evaluate the protective effect on glycemic control against impaired diabetic wound healing using a diabetic rat model. We investigated the wound healing process and effect on the impaired wound repair by glycemic control in the Spontaneously Diabetic Torii (SDT) fatty rat, which is a new animal model of obese type 2 diabetes and may be a good model for study impaired wound healing...
February 2018: Medical Archives
https://www.readbyqxmd.com/read/29412121/sodium-glucose-cotransporter-2-inhibitors-impact-on-body-weight-and-blood-pressure-compared-with-other-antidiabetic-drugs
#6
Konstantinos Imprialos, Konstantinos Stavropoulos, Nikiforos Stavropoulos, Dimitrios Patoulias, Konstantinos Petidis, Charalampos Grassos, Kyriakos Dimitriadis, Constantinos Tsioufis
BACKGROUND: Sodium-glucose co-transporters 2 inhibitors have emerged as a novel antidiabetic class of drugs offering significant ameliorating effects on a variety of cardiovascular risk factors, secondary to their mechanism of action, including blood pressure and body weight. OBJECTIVE: The purpose of this article is to discuss available data on the impact of SGLT-2 inhibitors on blood pressure and body weight compared with other available antidiabetic drugs and to present potential mechanisms mediating these effects...
February 6, 2018: Cardiovascular & Hematological Disorders Drug Targets
https://www.readbyqxmd.com/read/29402406/secretion-of-glp-1-but-not-gip-is-potently-stimulated-by-luminal-d-allulose-d-psicose-in-rats
#7
Masaki Hayakawa, Tohru Hira, Masako Nakamura, Tetsuo Iida, Yuka Kishimoto, Hiroshi Hara
Glucagon-like peptide 1 (GLP-1), an incretin gastrointestinal hormone, is secreted when stimulated by nutrients including metabolizable sugars such as glucose and fructose. d-Allulose (allulose), also known as d-psicose, is a C-3 isomer of d-fructose and a rare sugar with anti-diabetic or anti-obese effects in animal models. In the present study, we examined whether an oral administration of allulose could stimulate GLP-1 secretion in rats, and investigated the underlying mechanisms. Oral, but not intraperitoneal, administration of allulose (0...
February 2, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29372664/sodium-glucose-co-transporter-2-inhibitors-and-cardiovascular-outcomes-a-systematic-review-and-meta-analysis
#8
Muhammad Shariq Usman, Tariq Jamal Siddiqi, Muhammad Mustafa Memon, Muhammad Shahzeb Khan, Wasiq Faraz Rawasia, Muhammad Talha Ayub, Jayakumar Sreenivasan, Yasmeen Golzar
Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors...
January 1, 2018: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/29370424/effects-of-the-sodium-glucose-co-transporter-2-inhibitor-dapagliflozin-in-patients-with-type-2-diabetes-and-stages-3b-4-chronic-kidney-disease
#9
Claire C J Dekkers, David C Wheeler, C David Sjöström, Bergur V Stefansson, Valerie Cain, Hiddo J L Heerspink
Background: The sodium-glucose co-transporter 2 inhibitor dapagliflozin decreases haemoglobin A1c (HbA1c), body weight, blood pressure (BP) and urinary albumin:creatinine ratio (UACR) in patients with type 2 diabetes. The efficacy and safety of this drug have not been properly defined in patients with type 2 diabetes and Stages 3b-4 chronic kidney disease (CKD). Methods: In a pooled analysis of 11 phase 3 randomized controlled clinical trials, we determined least square mean changes in HbA1c, body weight, BP, estimated glomerular filtration rate (eGFR) and UACR over 102 weeks in patients with type 2 diabetes and an eGFR between 12 to less than 45 mL/min/1...
January 23, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29361669/sglt2-inhibition-in-a-kidney-with-reduced-nephron-number-modeling-and-analysis-of-solute-transport-and-metabolism
#10
Anita T Layton, Volker Vallon
Sodium-glucose co-transporter 2 (SGLT2) inhibitors enhance urinary glucose, Na+ and fluid excretion and lower hyperglycemia in diabetes by targeting Na+ and glucose reabsorption along the proximal convoluted tubule. A goal of this study is to predict the effects of SGLT2 inhibitors in diabetic and non-diabetic patients with chronic kidney disease. To that end, we employed computational rat kidney models to explore how SGLT2 inhibition affects renal solute transport and metabolism when nephron populations are normal or reduced...
January 17, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29359851/do-sodium-glucose-cotransporter-2-inhibitors-prevent-heart-failure-with-a-preserved-ejection-fraction-by-counterbalancing-the-effects-of-leptin-a-novel-hypothesis
#11
Milton Packer
Sodium-glucose transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis...
January 23, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29355315/inhibition-of-glucose-transport-by-tomatoside-a-a-tomato-seed-steroidal-saponin-through-the-suppression-of-glut2-expression-in-caco-2-cells
#12
Baorui Li, Yusuke Terazono, Naoto Hirasaki, Yuki Tatemichi, Emiko Kinoshita, Akio Obata, Toshiro Matsui
We investigated whether tomatoside A (5α-furostane-3β,22,26-triol-3-[O-β-D-glucopyranosyl (1→2)-β-D-glucopyranosyl (1→4)-β-D-galactopyranoside] 26-O-β-D-glucopyranoside), a tomato seed saponin, may play a role in the regulation of intestinal glucose transport in human intestinal Caco-2 cells. Tomatoside A could not penetrate through Caco-2 cell monolayers, as observed in the transport experiments using liquid chromatography-mass spectrometry. The treatment of cells with 10 μM tomatoside A for 3 h resulted in a 46...
January 22, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29348720/gintonin-absorption-in-intestinal-model-systems
#13
Byung-Hwan Lee, Sun-Hye Choi, Hyeon-Joong Kim, Sang-Deuk Park, Hyewhon Rhim, Hyoung-Chun Kim, Sung-Hee Hwang, Seung-Yeol Nah
Background: Recently, we identified a novel ginseng-derived lysophosphatidic acid receptor ligand, called gintonin. We showed that gintonin induces [Ca2+]i transient-mediated morphological changes, proliferation, and migration in cells expressing lysophosphatidic acid receptors and that oral administration of gintonin exhibits anti-Alzheimer disease effects in model mice. However, little is known about the intestinal absorption of gintonin. The aim of this study was to investigate gintonin absorption using two model systems...
January 2018: Journal of Ginseng Research
https://www.readbyqxmd.com/read/29344329/major-adverse-cardiovascular-event-reduction-with-glp-1-and-sglt2-agents-evidence-and-clinical-potential
#14
REVIEW
Michael E Røder
Treatment of patients with type 2 diabetes is directed against treating symptoms of hyperglycemia, minimizing the risk of hypoglycemia, and the risk of microvascular and macrovascular complications. The majority of patients with type 2 diabetes die from cardiovascular or cerebrovascular disease. Future therapies should therefore focus on reducing cardiovascular morbidity in this high-risk population. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are two drug classes with proven antihyperglycemic effect in type 2 diabetes...
January 2018: Therapeutic Advances in Chronic Disease
https://www.readbyqxmd.com/read/29341404/intra-and-inter-subject-variability-for-increases-in-serum-ketone-bodies-in-patients-with-type-2-diabetes-treated-with-the-sodium-glucose-co-transporter-2-inhibitor-canagliflozin
#15
David Polidori, Hiroaki Iijima, Maki Goda, Nobuko Maruyama, Nobuya Inagaki, Peter A Crawford
SGLT2 inhibitors have been associated with increased serum ketone bodies in patients with type 2 diabetes mellitus (T2DM). This analysis evaluated serum ketone body levels and variability in 1,278 Japanese patients with T2DM treated with canagliflozin 100 or 200 mg. Similar mean increases in ketone body concentrations of ~2-fold were seen with both canagliflozin doses. Median (interquartile range) percent change from baseline was 62% (0;180) for acetoacetate and 78% (2;236) for β-hydroxybutyrate. Approximately 2/3 of the variability in each ketone measure was attributed to intra-subject variability...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29327406/short-and-medium-term-efficacy-of-sodium-glucose-co-transporter-2-sglt-2-inhibitors-a-meta-analysis-of-randomized-clinical-trials
#16
Matteo Monami, Francesco Liistro, Alessia Scatena, Besmir Nreu, Edoardo Mannucci
AIMS: Sodium glucose co-transport-2 (SGLT-2) inhibitors reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. Aim of this meta-analysis is the systematic collection of available data from randomized trials, in order to establish the durability of the efficacy of SGLT-2 inhibitors on glycemic control and body mass index. METHODS: A meta-analysis was performed including all trials with a duration of at least 12 weeks, comparing SGLT-2 inhibitors with a non-SGLT-2 inhibitor agents in type 2 diabetes...
January 12, 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
#17
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/29320889/the-cardiovascular-effect-of-incretin-based-therapies-among-type-2-diabetes-a-systematic-review-and-network-meta-analysis
#18
Shanshan Wu, Andrea Cipriani, Zhirong Yang, Jun Yang, Ting Cai, Yang Xu, Xiaochi Quan, Yuan Zhang, Sanbao Chai, Feng Sun, Siyan Zhan
OBJECTIVE: To evaluate the comparative cardiovascular safety of incretin-based therapies in patients with type 2 diabetes mellitus (T2DM). METHODS: Medline, Embase, the Cochrane Library and www.clinicaltrials.gov were searched for randomized controlled trials (RCTs) with duration≥12 weeks. Network meta-analysis was performed, followed by subgroup analysis and meta-regression. The Grading of Recommendations Assessment, Development and Evaluation system was used to assess the quality of evidence...
January 10, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29316197/tofogliflozin-decreases-body-fat-mass-and-improves-peripheral-insulin-resistance
#19
Ren Matsuba, Ikuro Matsuba, Mototsugu Shimokawa, Yoshio Nagai, Yasushi Tanaka
The impact of tofogliflozin, a sodium glucose transporter 2 inhibitor, on peripheral glucose uptake in patients with type 2 diabetes mellitus (T2DM) was investigated by the hyperinsulinemic-euglycemic clamp method in a single-arm, open-label study. The following parameters were compared between before and after tofogliflozin administration for 12 weeks in 16 T2DM patients using dipeptidyl peptidase 4 inhibitors: body weight, blood pressure, glucose metabolism, liver function, lipid profile, and body composition...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29313267/impact-of-canagliflozin-treatment-on-health-related-quality-of-life-among-people-with-type-2-diabetes-mellitus-a-pooled-analysis-of-patient-reported-outcomes-from-randomized-controlled-trials
#20
Jennifer Cai, Linda M Delahanty, Sydney Akapame, April Slee, Shana Traina
BACKGROUND: Evidence from patient-reported outcomes in clinical trials may explain health-related behaviors observed in the real world. OBJECTIVE: The purpose of this analysis was to evaluate the effect of treatment with canagliflozin, a sodium glucose co-transporter 2 inhibitor, compared with placebo or sitagliptin on health-related quality-of-life outcomes in participants with type 2 diabetes mellitus from the clinical development program. METHODS: Patient-reported outcomes data from four randomized controlled trials of canagliflozin (n = 2536) were pooled and analyzed to evaluate participants' interest in continuing study medication; satisfaction with weight; and physical, mental, and emotional health after 26-52 weeks of treatment with canagliflozin vs...
January 8, 2018: Patient
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