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Sotagliflozin

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https://www.readbyqxmd.com/read/28899222/effects-of-sotagliflozin-added-to-insulin-in-patients-with-type-1-diabetes
#1
Satish K Garg, Robert R Henry, Phillip Banks, John B Buse, Melanie J Davies, Gregory R Fulcher, Paolo Pozzilli, Diane Gesty-Palmer, Pablo Lapuerta, Rafael Simó, Thomas Danne, Darren K McGuire, Jake A Kushner, Anne Peters, Paul Strumph
Background In most patients with type 1 diabetes, adequate glycemic control is not achieved with insulin therapy alone. We evaluated the safety and efficacy of sotagliflozin, an oral inhibitor of sodium-glucose cotransporters 1 and 2, in combination with insulin treatment in patients with type 1 diabetes. Methods In this phase 3, double-blind trial, which was conducted at 133 centers worldwide, we randomly assigned 1402 patients with type 1 diabetes who were receiving treatment with any insulin therapy (pump or injections) to receive sotagliflozin (400 mg per day) or placebo for 24 weeks...
September 13, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28872070/hydrogen-bonded-structures-and-interaction-energies-in-two-forms-of-the-sglt-2-inhibitor-sotagliflozin
#2
Thomas Gelbrich, Verena Adamer, Marijan Stefinovic, Andrea Thaler, Ulrich J Griesser
The sotagliflozin molecule exhibits two fundamentally different molecular conformations in form 1 {systematic name: (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxybenzyl)phenyl]-6-(methylsulfanyl)tetrahydro-2H-pyran-3,4,5-triol, C21H25ClO5S, (I)} and the monohydrate [C21H25ClO5S·H2O, (II)]. Both crystals display hydrogen-bonded layers formed by intermolecular interactions which involve the three -OH groups of the xyloside fragment of the molecule. The layer architectures of (I) and (II) contain a non-hydrogen-bonded molecule-molecule interaction along the short crystallographic axis (a axis) whose total PIXEL energy exceeds that of each hydrogen-bonded molecule-molecule pair...
September 1, 2017: Acta Crystallographica. Section C, Structural Chemistry
https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#3
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28387957/molecular-interaction-of-anti-diabetic-drugs-with-acetylcholinesterase-and-sodium-glucose-co-transporter-2
#4
Shazi Shakil
Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD) are the two disorders which are known to share pertinent pathological and therapeutic links. Sodium glucose co-transporter-2 (SGLT2) and Acetylcholinesterase (AChE) are established inhibition targets for T2DM and AD treatments, respectively. Reports suggest that anti-diabetic drugs could be used for AD treatment also. The present study used molecular docking by Autodock4.2 using our "Click-By-Click"-protocol, Ligplot1.4.3 and "change in accessible surface area (ΔASA)-calculations" to investigate the binding of two investigational anti-diabetic drugs, Ertugliflozin and Sotagliflozin to an established target (SGLT2) and a research target (human brain AChE)...
April 7, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/26548423/sotagliflozin-as-a-potential-treatment-for-type-2-diabetes-mellitus
#5
REVIEW
Bertrand Cariou, Bernard Charbonnel
INTRODUCTION: SGLT1 is the primary transporter responsible for the absorption of glucose and galactose in the intestine, while SGLT2 and SGLT1 are both involved in the renal reabsorption of glucose. SGLT2 inhibitors are a new class of oral antidiabetic drugs, acting by increasing urinary glucose excretion (UGE). They offer the advantages of a reduced risk of hypoglycaemia, a decrease in body weight and blood pressure and an efficacy at all stages of type 2 diabetes (T2DM). AREAS COVERED: Herein, the authors focus specifically on sotagliflozin (LX4211), the first-in-class dual SGLT1/SGLT2 inhibitor...
2015: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26484403/the-emerging-role-of-adjunctive-noninsulin-antihyperglycemic-therapy-in-the-management-of-type-1-diabetes
#6
REVIEW
Bruce W Bode, Satish K Garg
OBJECTIVE: Review available data on adjunctive therapies for type 1 diabetes (T1D), with a special focus on newer antihyperglycemic agents. METHODS: Published data on hypoglycemia, obesity, mortality, and goal attainment in T1D were reviewed to determine unmet therapeutic needs. PubMed databases and abstracts from recent diabetes meetings were searched using the term "type 1 diabetes" and the available and investigational sodium-glucose cotransporter (SGLT) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 inhibitors, and metformin...
February 2016: Endocrine Practice
https://www.readbyqxmd.com/read/26049551/sotagliflozin-a-dual-sglt1-and-sglt2-inhibitor-as-adjunct-therapy-to-insulin-in-type-1-diabetes
#7
RANDOMIZED CONTROLLED TRIAL
Arthur T Sands, Brian P Zambrowicz, Julio Rosenstock, Pablo Lapuerta, Bruce W Bode, Satish K Garg, John B Buse, Phillip Banks, Rubina Heptulla, Marc Rendell, William T Cefalu, Paul Strumph
OBJECTIVE: To assess the safety and efficacy of dual sodium-glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS: We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment. RESULTS: In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32...
July 2015: Diabetes Care
https://www.readbyqxmd.com/read/25759591/sotagliflozin-improves-glycemic-control-in-nonobese-diabetes-prone-mice-with-type-1-diabetes
#8
David R Powell, Deon Doree, Sabrina Jeter-Jones, Zhi-Ming Ding, Brian Zambrowicz, Arthur Sands
PURPOSE: Oral agents are needed that improve glycemic control without increasing hypoglycemic events in patients with type 1 diabetes (T1D). Sotagliflozin may meet this need, because this compound lowers blood glucose through the insulin-independent mechanisms of inhibiting kidney SGLT2 and intestinal SGLT1. We examined the effect of sotagliflozin on glycemic control and rate of hypoglycemia measurements in T1D mice maintained on a low daily insulin dose, and compared these results to those from mice maintained in better glycemic control with a higher daily insulin dose alone...
2015: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/25690134/development-of-sotagliflozin-a-dual-sodium-dependent-glucose-transporter-1-2-inhibitor
#9
REVIEW
Pablo Lapuerta, Brian Zambrowicz, Paul Strumph, Arthur Sands
The sodium-dependent glucose transporter 2 (SGLT2) inhibitors are an important emerging class for the treatment of diabetes. Development of SGLT2 inhibitors has been oriented around a desire for high selectivity for the SGLT2 protein relative to the SGLT1 protein. More recently, genetic and pharmacology research in mice has indicated that gastrointestinal SGLT1 inhibition may also be an appropriate therapeutic target to treat diabetes. Combining SGLT1 and SGLT2 inhibition in a single molecule would provide complementary insulin-independent mechanisms to treat diabetes...
March 2015: Diabetes & Vascular Disease Research
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