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SGLT-2 Therapies

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10 papers 0 to 25 followers
By Ehud Ur Professor and Head, Endocrinology, UBC, Vancouver
André J Scheen
Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycemia by increasing urinary glucose excretion. They have been evaluated in patients with type 2 diabetes treated with diet/exercise, metformin, dual oral therapy or insulin. Three agents are available in Europe and the USA (canagliflozin, dapagliflozin, empagliflozin) and others are commercialized in Japan or in clinical development. SGLT2 inhibitors reduce glycated hemoglobin, with a minimal risk of hypoglycemia. They exert favorable effects beyond glucose control with consistent body weight, blood pressure, and serum uric acid reductions...
October 2016: Current Diabetes Reports
Jason H Y Wu, Celine Foote, Juuso Blomster, Tadashi Toyama, Vlado Perkovic, Johan Sundström, Bruce Neal
BACKGROUND: In patients with type 2 diabetes, sodium-glucose cotransporter-2 (SGLT2) inhibitors are known to reduce glucose concentrations, blood pressure, and weight, but to increase LDL cholesterol and the incidence of urogenital infections. Protection against cardiovascular events has also been reported, as have possible increased risks of adverse outcomes such as ketoacidosis and bone fracture. We aimed to establish the effects of SGLT2 inhibitors on cardiovascular events, death, and safety outcomes in adults with type 2 diabetes, both overall and separately for individual drugs...
May 2016: Lancet Diabetes & Endocrinology
Naveed Sattar, James McLaren, Søren L Kristensen, David Preiss, John J McMurray
While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30-40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such trials to have reported, as a precursor to understanding why the EMPA-REG Outcomes results came as a surprise...
July 2016: Diabetologia
Yehuda Handelsman, Robert R Henry, Zachary T Bloomgarden, Sam Dagogo-Jack, Ralph A DeFronzo, Daniel Einhorn, Ele Ferrannini, Vivian A Fonseca, Alan J Garber, George Grunberger, Derek LeRoith, Guillermo E Umpierrez, Matthew R Weir
AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology DKA = diabetic ketoacidosis EMA = European Medicines Agency FDA = U.S. Food and Drug Administration SGLT-2 = sodium glucosecotransporter 2 T1D = type 1 diabetes T2D = type 2 diabetes.
June 2016: Endocrine Practice
Yasushi Honda, Kento Imajo, Takayuki Kato, Takaomi Kessoku, Yuji Ogawa, Wataru Tomeno, Shingo Kato, Hironori Mawatari, Koji Fujita, Masato Yoneda, Satoru Saito, Atsushi Nakajima
BACKGROUND & AIMS: In recent years, nonalcoholic steatohepatitis (NASH) has become a considerable healthcare burden worldwide. Pathogenesis of NASH is associated with type 2 diabetes mellitus (T2DM) and insulin resistance. However, a specific drug to treat NASH is lacking. We investigated the effect of the selective sodium glucose cotransporter 2 inhibitor (SGLT2I) ipragliflozin on NASH in mice. METHODS: We used the Amylin liver NASH model (AMLN), which is a diet-induced model of NASH that results in obesity and T2DM...
2016: PloS One
Hidekatsu Yanai, Hisayuki Katsuyama, Hidetaka Hamasaki, Hiroki Adachi, Sumie Moriyama, Reo Yoshikawa, Akahito Sako
The new drug for type 2 diabetes, the sodium-glucose cotransporter 2 (SGLT-2) inhibitor, is reversible inhibitor of SGLT-2, leading to reduction of renal glucose reabsorption and decrease of plasma glucose, in an insulin-independent manner. In addition to glucose control, the management of coronary risk factors is very important for patients with diabetes. Here we reviewed published articles about the possible anti-atherosclerotic effects beyond glucose lowering of the SGLT-2 inhibitors. We searched by using Pubmed, and found 770 published articles about SGLT-2 inhibitors...
January 2016: Journal of Clinical Medicine Research
Shirong Qiang, Yusuke Nakatsu, Yasuyuki Seno, Midori Fujishiro, Hideyuki Sakoda, Akifumi Kushiyama, Keiichi Mori, Yasuka Matsunaga, Takeshi Yamamotoya, Hideaki Kamata, Tomoichiro Asano
BACKGROUND: Insulin resistance with elevated glucose is a risk factor for non-alcoholic steatohepatitis (NASH). We investigated the effects of the sodium glucose cotransporter 2 (SGLT2) inhibitor luseogliflozin on NASH development using a rodent model. METHODS: Mice were treated with both nicotinamide and streptozotocin (NA/STZ) to reduce insulin secretory capacity, and then fed a high fat diet containing trans fatty acids (HFDT) for 8 weeks. The NA/STZ HFDT-fed mice were divided into two groups, either treated with luseogliflozin or untreated, during this period...
2015: Diabetology & Metabolic Syndrome
Caroline Bonner, Julie Kerr-Conte, Valéry Gmyr, Gurvan Queniat, Ericka Moerman, Julien Thévenet, Cédric Beaucamps, Nathalie Delalleau, Iuliana Popescu, Willy J Malaisse, Abdullah Sener, Benoit Deprez, Amar Abderrahmani, Bart Staels, François Pattou
Type 2 diabetes (T2D) is characterized by chronic hyperglycemia resulting from a deficiency in insulin signaling, because of insulin resistance and/or defects in insulin secretion; it is also associated with increases in glucagon and endogenous glucose production (EGP). Gliflozins, including dapagliflozin, are a new class of approved oral antidiabetic agents that specifically inhibit sodium-glucose co-transporter 2 (SGLT2) function in the kidney, thus preventing renal glucose reabsorption and increasing glycosuria in diabetic individuals while reducing hyperglycemia...
May 2015: Nature Medicine
Robert R Henry, Julio Rosenstock, Steven Edelman, Sunder Mudaliar, Alexandros-Georgios Chalamandaris, Sreeneeranj Kasichayanula, Allyson Bogle, Nayyar Iqbal, James List, Steven C Griffen
OBJECTIVE: Insulin adjustments to maintain glycemic control in individuals with type 1 diabetes often lead to wide glucose fluctuations, hypoglycemia, and increased body weight. Dapagliflozin, an insulin-independent sodium-glucose cotransporter 2 (SGLT2) inhibitor, increases glucosuria and reduces hyperglycemia in individuals with type 2 diabetes. The primary objective of this study was to assess short-term safety of dapagliflozin in combination with insulin; secondary objectives included pharmacokinetic, pharmacodynamic, and efficacy parameters...
March 2015: Diabetes Care
Bruce Neal, Vlado Perkovic, Dick de Zeeuw, Kenneth W Mahaffey, Greg Fulcher, Kirk Ways, Mehul Desai, Wayne Shaw, George Capuano, Maria Alba, Joel Jiang, Frank Vercruysse, Gary Meininger, David Matthews
OBJECTIVE: There are limited data about the effects of sodium-glucose cotransporter 2 inhibitors when used with insulin. We report the efficacy and safety of canagliflozin in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS: The CANagliflozin CardioVascular Assessment Study is a double-blind, placebo-controlled study that randomized participants to placebo, canagliflozin 100 mg, or canagliflozin 300 mg once daily, added to a range of therapies...
March 2015: Diabetes Care
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