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Sodium glucose transport inhibitors

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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
#1
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/28427104/pharmacokinetics-and-pharmacodynamics-of-tofogliflozin-a-selective-sglt2-inhibitor-in-healthy-male-subjects
#2
Nahoko Kasahara-Ito, Hiroyuki Fukase, Yoichiro Ogama, Tomohisa Saito, Yasuhiro Ohba, Sumire Shimada, Yasuki Takano, Tomoko Ichihara, Kimio Terao, Noboru Nakamichi, Yuji Kumagai, Sachiya Ikeda
Tofogliflozin is a selective oral inhibitor of sodium-glucose co-transporter 2 for treatment of type 2 diabetes mellitus. The pharmacokinetics, pharmacodynamics, and safety of tofogliflozin were investigated in healthy male subjects. Three studies were conducted: single-ascending dose study (10-640 mg) in 56 Japanese and 24 Caucasian subjects; multiple-ascending dose study (2.5-80 mg once daily for 7 days) in 24 Japanese subjects; and food-effect study (20-40 mg) in 30 Japanese subjects. Tofogliflozin was absorbed rapidly and eliminated from the systemic circulation with a t1/2 of 5-6 h...
April 20, 2017: Drug Research
https://www.readbyqxmd.com/read/28422431/effect-of-empagliflozin-on-tacrolimus-induced-pancreas-islet-dysfunction-and-renal-injury
#3
J Jin, L Jin, K Luo, S W Lim, B H Chung, C W Yang
An inhibitor of sodium glucose co-transporter type 2 (SGLT-2) is recommended in type 2 diabetes mellitus (DM) but its use is still undetermined in Tacrolimus (TAC)-induced DM. We evaluated the effect of empagliflozin (Em) on TAC-induced pancreatic islet dysfunction and renal injury in experimental model of TAC-induced DM and in vitro. TAC induced a two-fold increase in SGLT-2 expression, while Em decreased SGLT-2 expression and further increased urinary glucose excretion compared to the TAC group. Em reduced hyperglycemia and increased plasma insulin level, pancreatic islet size and glucose-stimulated insulin secretion (GSIS) compared to the TAC group...
April 19, 2017: American Journal of Transplantation
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
#4
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 2/1/2014-6/30/2014 were identified from the QuintilesIMS PharMetrics Plus Database...
April 18, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28410751/mizagliflozin-a-novel-selective-sglt1-inhibitor-exhibits-potential-in-the-amelioration-of-chronic-constipation
#5
Toshihiro Inoue, Masaaki Takemura, Nobuhiko Fushimi, Yoshikazu Fujimori, Tomoya Onozato, Takao Kurooka, Tetsuya Asari, Hiroo Takeda, Mamoru Kobayashi, Hironori Nishibe, Masayuki Isaji
Chronic constipation is a highly common functional gastrointestinal disorder that adversely affects patient quality of life. At present, limited therapeutic options are available for the treatment of chronic constipation, which indicates the need for new therapeutic agents. Herein, we report the potential of mizagliflozin, a novel selective sodium glucose co-transporter 1 (SGLT1) inhibitor, for the amelioration of chronic constipation. Mizagliflozin's inhibitory activity against SGLTs was evaluated by an in vitro assay of cells transiently expressing SGLTs...
April 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28399981/efficacy-and-safety-of-sglt2-inhibitors-in-patients-with-type-1-diabetes-a-meta-analysis-of-randomized-controlled-trials
#6
Yang Yingying, Pan Hui, Wang Bo, Chen Shi, Zhu Huijuan
Objective To assess the efficiency and safety of a novel sodium-glucose co-transporter 2 (SGLT2) inhibitor-SGLT2 inhibitors, in combination with insulin for type 1 diabetes mellitus (T1DM). Methods We searched Medline, Embase, and the Cochrane Collaboration Library to identify the eligible studies published between January 2010 and July 2016 without restriction of language. The Food and Drug Administration (FDA) data and ClinicalTrials (http://www.clinicaltrials.gov) were also searched. The included studies met the following criteria: randomized controlled trials; T1DM patients aged between 18 and 65 years old; patients were treated with insulin plus SGLT2 inhibitors for more than 2 weeks; patients' glycosylated hemoglobin (HbA1c) levels were between 7% and 12%...
April 10, 2017: Chinese Medical Sciences Journal, Chung-kuo i Hsüeh K'o Hsüeh Tsa Chih
https://www.readbyqxmd.com/read/28395981/mechanisms-linking-empagliflozin-to-cardiovascular-and-renal-protection
#7
Pasquale Perrone-Filardi, Angelo Avogaro, Enzo Bonora, Furio Colivicchi, Paola Fioretto, Aldo Pietro Maggioni, Giorgio Sesti, Ele Ferrannini
In patients with type 2 diabetes mellitus (T2DM), the main cause of morbidity and mortality is cardiovascular (CV) disease. Diabetic kidney disease, which develops in approximately 40% of patients with T2DM, further increases the risk of CV-related morbidity and mortality. The sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin, which provides effective glycaemic control as either monotherapy or as an add-on to other glucose-lowering agents in patients with T2DM, was also shown to improve CV and renal outcomes in the large, randomised, placebo-controlled EMPA-REG OUTCOME trial in patients with T2DM at high risk of CV events...
March 23, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28395380/streptozotocin-treated-high-fat-fed-mice-a-new-type-2-diabetes-model-used-to-study-canagliflozin-induced-alterations-in-lipids-and-lipoproteins
#8
Tian Yu, Mitchell J Sungelo, Ira J Goldberg, Hong Wang, Robert H Eckel
The pharmacological effects of type 2 diabetes (T2DM) medications on lipoprotein metabolism are difficult to assess in preclinical models because those created failure to replicate the human condition in which insulin deficiency is superimposed on obesity-related insulin resistance. To create a better model, we fed mice with high fat (HF) diet and treated the animals with low dose streptozotocin (STZ) to mimic T2DM. We used this model to evaluate the effects of canagliflozin (CANA), a drug that reduces plasma glucose by inhibiting the sodium-glucose transporter 2 (SGLT2), which mediates ~90% of renal glucose reabsorption] on lipid and lipoprotein metabolism...
April 10, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28395363/natural-products-as-lead-compounds-for-sodium-glucose-cotransporter-sglt-inhibitors
#9
Wolfgang Blaschek
Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs)...
April 10, 2017: Planta Medica
https://www.readbyqxmd.com/read/28393583/spotlight-on-canagliflozin-300-review-of-its-efficacy-and-an-indirect-comparison-to-other-sglt-2-inhibitors-and-long-acting-glp-1-receptor-agonists
#10
Awadhesh Kumar Singh, Ritu Singh
Both sodium-glucose co-transporter-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been consistently found to lower blood glucose, body weight and systolic blood pressure (SBP) in patients with type 2 diabetes mellitus (T2DM). While all the SGLT-2Is inhibit glucose reabsorption by blocking SGLT-2 receptor in kidney, dose-dependently, the highest licensed dose of canagliflozin 300-mg has an additional ability to inhibit SGLT-1 receptor in intestine transiently, that may lead to additional inhibition of prandial glucose absorption, unlike other approved highly selective SGLT-2Is...
April 17, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#11
M Kim, E J Lee, H M Shin, H S Jung, T K Kim, T N Kim, M J Kwon, S H Lee, B D Rhee, J H Park
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia...
April 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28385801/mechanisms-controlling-glucose-induced-glp-1-secretion-in-human-small-intestine
#12
Emily W Sun, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven L Due, David A Wattchow, Christopher K Rayner, Adam M Deane, Richard L Young, Damien J Keating
Intestinal glucose stimulates secretion of the incretin hormone glucagon-like peptide 1 (GLP-1). The mechanisms underlying this pathway have not been fully investigated in humans. In this study, we showed that a 30 minute intraduodenal glucose infusion activated half of all duodenal L cells in humans. This infusion was sufficient to increase plasma GLP-1. With an ex vivo model using human gut tissue specimens, we showed a dose-responsive GLP-1 secretion in ileum at 200mM glucose or above. In ex vivo tissue from duodenum and ileum, but not colon, 300mM glucose potently stimulated GLP-1 release...
April 6, 2017: Diabetes
https://www.readbyqxmd.com/read/28379501/cardiovascular-effects-of-urate-lowering-therapies-in-patients-with-chronic-gout-a-systematic-review-and-meta-analysis
#13
Tony Zhang, Janet E Pope
Objectives.: To determine if urate-lowering treatment (ULT) in gout can reduce cardiovascular (CV) outcomes. Methods.: Randomized trials were searched for treatment with ULT in gout. Eligible trials had to report CV safety of a ULT. Potential medications included allopurinol, febuxostat, pegloticase, rasburicase, probenecid, benzbromarone, sulphinpyrazone, losartan, fenofibrate and sodium-glucose linked transporter 2 inhibitors. Results.: A total of 3084 citations were found, with 642 duplicates...
March 30, 2017: Rheumatology
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
#14
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
https://www.readbyqxmd.com/read/28375658/empagliflozin-linagliptin-single-pill-combination-therapy-for-patients-with-type-2-diabetes-mellitus
#15
Rajeev Kumar Jain
Type 2 diabetes mellitus (T2DM) is typically progressive, with sequential addition of therapies often needed to address increasing hyperglycemia over the disease course. Using treatments in combination may be preferred to sequential addition, as a means of providing a more rapid clinical response and potentially avoiding clinical inertia. In such cases, a single-pill combination can help to reduce pill burden. Although various single-pill combinations of oral glucose-lowering agents are available, empagliflozin/linagliptin was the first approved combination of a sodium glucose co-transporter 2 (SGLT2) inhibitor with a dipeptidyl peptidase 4 (DPP-4) inhibitor in the United States...
April 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28371205/efficacy-and-safety-of-tofogliflozin-in-japanese-patients-with-type-2-diabetes-mellitus-with-inadequate-glycaemic-control-on-insulin-therapy-j-step-ins-results-of-a-16-week-randomized-double-blind-placebo-controlled-multicentre-trial
#16
Yasuo Terauchi, Masahiro Tamura, Masayuki Senda, Ryoji Gunji, Kohei Kaku
AIMS: To assess the effects of 16 weeks of tofogliflozin (sodium/glucose co-transporter 2 (SGLT2) inhibitor) treatment versus placebo on glycosylated haemoglobin (HbA1c) levels in Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled with insulin monotherapy or insulin plus a dipeptidyl peptidase-4 (DPP-4) inhibitor. METHODS: This study comprises a 16-week, multicentre, double-blind, placebo-controlled period and a 36-week extension (NCT02201004)...
March 30, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28364032/sodium-glucose-transporter-2-inhibition-has-no-renoprotective-effects-on-non-diabetic-chronic-kidney-disease
#17
Qiuyue Ma, Stefanie Steiger, Hans-Joachim Anders
Sodium glucose transporter (SGLT)-2 inhibition has renoprotective effects in diabetic kidney disease. Whether similar effects can be achieved also in non-diabetic kidney disease is speculative. Chronic kidney disease was induced in C57BL/6N mice by feeding an oxalate-rich diet for 14 days, known to induce nephrocalcinosis-related tubular atrophy and interstitial fibrosis without directly affecting the glomerular compartment. Empagliflozin treatment started from day 0 of oxalate feeding had no effect on the decline of glomerular filtration rate, crystal deposition, blood urea nitrogen or serum creatinine levels on day 7 and 14...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28358310/intestinal-transport-characteristics-and-metabolism-of-c-glucosyl-dihydrochalcone-aspalathin
#18
Sandra Bowles, Elizabeth Joubert, Dalene de Beer, Johan Louw, Christel Brunschwig, Mathew Njoroge, Nina Lawrence, Lubbe Wiesner, Kelly Chibale, Christo Muller
Insight into the mechanisms of intestinal transport and metabolism of aspalathin will provide important information for dose optimisation, in particular for studies using mouse models. Aspalathin transportation across the intestinal barrier (Caco-2 monolayer) tested at 1-150 µM had an apparent rate of permeability (Papp) typical of poorly absorbed compounds (1.73 × 10(-6) cm/s). Major glucose transporters, sodium glucose linked transporter 1 (SGLT1) and glucose transporter 2 (GLUT2), and efflux protein (P-glycoprotein, PgP) (1...
March 30, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28352212/canagliflozin-in-the-treatment-of-type-2-diabetes-an-evidence-based-review-of-its-place-in-therapy
#19
REVIEW
Thomas Karagiannis, Eleni Bekiari, Apostolos Tsapas
INTRODUCTION: Deciding on an optimal medication choice for type 2 diabetes is often challenging, due to the increasing number of treatment options. Canagliflozin is a novel glucose-lowering agent belonging to sodium-glucose co-transporter 2 (SGLT2) inhibitors. AIM: The aim of this study was to examine and summarize the evidence based on the efficacy, safety, and cost-effectiveness of canagliflozin for type 2 diabetes. EVIDENCE REVIEW: Compared to placebo, canagliflozin 100 and 300 mg lower glycated hemoglobin (HbA1c) by ~0...
2017: Core Evidence
https://www.readbyqxmd.com/read/28349443/cost-effectiveness-of-liraglutide-versus-dapagliflozin-for-the-treatment-of-patients-with-type%C3%A2-2-diabetes-mellitus-in-the-uk
#20
Gabriela Vega-Hernandez, Radek Wojcik, Max Schlueter
INTRODUCTION: To date there is a lack of economic analysis comparing glucagon-like peptide-1 receptor agonists (GLP-1RAs) to sodium-glucose co-transporter 2 inhibitors (SGLT-2i) for the treatment of type 2 diabetes mellitus (T2DM). Liraglutide and dapagliflozin are the most commonly prescribed GLP-1RA and SGLT-2i in the UK. This analysis investigated the cost-effectiveness of liraglutide 1.2 and 1.8 mg/day compared to dapagliflozin 10 mg/day for the treatment of T2DM in the UK in patients on dual and triple antidiabetic therapy...
March 27, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
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