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SGLT-2 Therapies

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22 papers 0 to 25 followers
By Ehud Ur Professor and Head, Endocrinology, UBC, Vancouver
Helena W Rodbard, Anne L Peters, April Slee, Anjun Cao, Shana B Traina, Maria Alba
OBJECTIVE: To assess the effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, on glycemic parameters and measures of glucose variability assessed by a 9-point self-monitoring blood glucose (SMBG) and continuous glucose monitoring (CGM) profiles, and patient-reported outcomes as an add-on to insulin among participants with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this randomized, double-blind study, 351 participants received canagliflozin 100 or 300 mg or placebo for 18 weeks...
February 2017: Diabetes Care
Rory J McCrimmon, Robert R Henry
Non-insulin adjunct therapies in type 1 diabetes have been proposed as a means of improving glycaemic control and reducing risk of hypoglycaemia. Evidence to support this approach is, however, scant and few pharmacological agents have proved effective enough to become part of routine clinical care. Recent short-term Phase II trials and 24 week Phase III trials provide initial support for the use of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes. Two international, multicentre, randomised, controlled clinical trials, Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 Diabetes (DEPICT-1) and inTandem3, have reported that SGLT inhibition with dapagliflozin and sotagliflozin, respectively, confer additional benefits in terms of a 5-6 mmol/mol (0...
October 2018: Diabetologia
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...
December 14, 2017: New England Journal of Medicine
Halis Kaan Akturk, Amanda Rewers, Satish K Garg
PURPOSE OF REVIEW: To identify and evaluate the recent trials of sodium-glucose cotransporter 1 and 2 (SGLT1 and SGLT2, respectively) inhibitor use in patients with type 1 diabetes (T1D). SGLT-2 inhibitors have been approved by the Food and Drug Administration (FDA) and are effectively used in the treatment of type 2 diabetes (T2D). However, many studies (phase I-III) have validated their effects beyond improving glycemic control and have shown potential adjunctive use in adult patients with T1D treated with insulin therapy alone...
August 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Julio Rosenstock, Jan Marquard, Lori M Laffel, Dietmar Neubacher, Stefan Kaspers, David Z Cherney, Bernard Zinman, Jay S Skyler, Jyothis George, Nima Soleymanlou, Bruce A Perkins
OBJECTIVE: To evaluate the safety and efficacy of empagliflozin 10- and 25-mg doses plus a unique lower dose (2.5 mg) as adjunct to intensified insulin in patients with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: The EASE (Empagliflozin as Adjunctive to inSulin thErapy) program ( N = 1,707) included two double-blind, placebo-controlled phase 3 trials: EASE-2 with empagliflozin 10 mg ( n = 243), 25 mg ( n = 244), and placebo ( n = 243), 52-week treatment; and EASE-3 with empagliflozin 2...
December 2018: Diabetes Care
Silvio E Inzucchi, Mikhail Kosiborod, David Fitchett, Christoph Wanner, Uwe Hehnke, Stefan Kaspers, Jyothis T George, Bernard Zinman
No abstract text is available yet for this article.
October 23, 2018: Circulation
Richard J MacIsaac, Melissa H Lee, Sybil A McAuley, Glenn M Ward, David N O'Neal
No abstract text is available yet for this article.
December 2018: Annals of Translational Medicine
Chantal Mathieu, Paresh Dandona, Pieter Gillard, Peter Senior, Christoph Hasslacher, Eiichi Araki, Marcus Lind, Stephen C Bain, Serge Jabbour, Niki Arya, Lars Hansen, Fredrik Thorén, Anna Maria Langkilde
OBJECTIVE: This 24-week, double-blinded, phase 3 clinical trial (DEPICT-2;, NCT02460978) evaluated efficacy and safety of dapagliflozin as adjunct therapy to adjustable insulin in patients with inadequately controlled type 1 diabetes (HbA1c 7.5-10.5%). RESEARCH DESIGN AND METHODS: Patients were randomized 1:1:1 to dapagliflozin 5 mg ( n = 271), dapagliflozin 10 mg ( n = 270), or placebo ( n = 272) plus insulin. Insulin dose was adjusted by investigators according to self-monitored glucose readings, local guidance, and individual circumstances...
September 2018: Diabetes Care
Thomas Danne, Satish Garg, Anne L Peters, John B Buse, Chantal Mathieu, Jeremy H Pettus, Charles M Alexander, Tadej Battelino, F Javier Ampudia-Blasco, Bruce W Bode, Bertrand Cariou, Kelly L Close, Paresh Dandona, Sanjoy Dutta, Ele Ferrannini, Spiros Fourlanos, George Grunberger, Simon R Heller, Robert R Henry, Martin J Kurian, Jake A Kushner, Tal Oron, Christopher G Parkin, Thomas R Pieber, Helena W Rodbard, Desmond Schatz, Jay S Skyler, William V Tamborlane, Koutaro Yokote, Moshe Phillip
Sodium glucose cotransporter (SGLT) inhibitors are new oral antidiabetic medications shown to effectively reduce glycated hemoglobin (A1C) and glycemic variability, blood pressure and body weight without intrinsic properties to cause hypoglycemia in people with type 1 diabetes. However, recent studies, particularly in individuals with type 1 diabetes, have demonstrated increases in the absolute risk of diabetic ketoacidosis (DKA). Some cases presented with near-normal blood glucose levels or mild hyperglycemia, complicating the recognition/diagnosis of DKA and potentially delaying treatment...
February 6, 2019: Diabetes Care
Yuliya Lytvyn, Petter Bjornstad, Jacob A Udell, Julie A Lovshin, David Z I Cherney
Despite current established therapy, heart failure (HF) remains a leading cause of hospitalization and mortality worldwide. Novel therapeutic targets are therefore needed to improve the prognosis of patients with HF. The EMPA-REG OUTCOME trial ([Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) demonstrated significant reductions in mortality and HF hospitalization risk in patients with type 2 diabetes mellitus (T2D) and cardiovascular disease with the antihyperglycemic agent, empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor...
October 24, 2017: Circulation
Priscilla Hollander, Harold E Bays, Julio Rosenstock, Mary Ellen Frustaci, Albert Fung, Frank Vercruysse, Ngozi Erondu
OBJECTIVE: To assess the efficacy and safety of coadministration of canagliflozin (CANA) and phentermine (PHEN) compared with placebo (PBO) and CANA or PHEN monotherapies in individuals who were overweight and obese without type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week, phase 2a, randomized, double-blind, PBO-controlled, multicenter, parallel-group study enrolled individuals who were obese or overweight without type 2 diabetes ( N = 335, aged 18-65 years, BMI ≥30 to <50 kg/m2 or BMI ≥27 to <50 kg/m2 with hypertension and/or dyslipidemia)...
May 2017: Diabetes Care
Ralph A DeFronzo, Luke Norton, Muhammad Abdul-Ghani
The kidney has a pivotal role in maintaining glucose homeostasis by using glucose as a metabolic fuel, by producing glucose through gluconeogenesis, and by reabsorbing all filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In patients with diabetes, the maximum glucose reabsorptive capacity (TmG ) of the kidney, as well as the threshold for glucose spillage into the urine, are elevated, contributing to the pathogenesis of hyperglycaemia. By reducing the TmG and, more importantly, the threshold of glucosuria, SGLT2 inhibitors enhance glucose excretion, leading to a reduction in fasting and postprandial plasma glucose levels and improvements in both insulin secretion and insulin sensitivity...
January 2017: Nature Reviews. Nephrology
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
2015-04-24 20:31:05
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