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Canagliflozin

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https://www.readbyqxmd.com/read/28926495/bolstering-your-armamentarium-with-sglt2-inhibitors
#1
Lucia M Novak, Davida F Kruger
Sodium-glucose cotransporter-2 inhibitors have a unique mechanism of action in the kidneys that causes glucosuria, which lowers plasma glucose. They are also associated with reduced body weight and BP, and a low incidence of hypoglycemia. This article reviews the pharmacologic profiles and clinical implications of canagliflozin, dapagliflozin, and empagliflozin.
October 18, 2017: Nurse Practitioner
https://www.readbyqxmd.com/read/28916336/renal-tubular-and-adrenal-medullary-tumors-in-the-2-year-rat-study-with-canagliflozin-confirmed-to-be-secondary-to-carbohydrate-glucose-malabsorption-in-the-15-month-mechanistic-rat-study
#2
Sandra De Jonghe, Mark D Johnson, Rao N V S Mamidi, Petra Vinken, Bianca Feyen, Godelieve Lammens, Jim Proctor
During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet...
September 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28898514/risk-of-lower-extremity-amputations-in-patients-with-type-2-diabetes-mellitus-treated-with-sglt2-inhibitors-in-the-united-states-a-retrospective-cohort-study
#3
Zhong Yuan, Frank J DeFalco, Patrick B Ryan, Martijn J Schuemie, Paul E Stang, Jesse A Berlin, Mehul Desai, Norm Rosenthal
AIMS: To examine the incidence of amputation in patients with type 2 diabetes mellitus (T2DM) treated with sodium glucose co-transporter 2 inhibitors (SGLT2i) overall, and canagliflozin specifically, compared with non-SGLT2i antihyperglycemic agents (AHAs). MATERIALS AND METHODS: Patients with T2DM newly exposed to SGLT2i or non-SGLT2i AHAs were identified using the Truven MarketScan database. The incidence of below-knee lower extremity (BKLE) amputation was calculated for patients treated with SGLT2i, canagliflozin, or non-SGLT2i AHAs...
September 12, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#4
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28879786/pharmacological-management-of-type-2-diabetes-what-s-new-in-2017
#5
André J Scheen
Introduction Novelties in the management of type 2 diabetes are dominated by the commercialisation of new glucose-lowering agents, which offer alternatives to older antidiabetic medications, and by the publication of several prospective placebo-controlled outcome trials, which demonstrated not only cardiovascular safety but also cardiovascular and renal protection with some new medications. Areas covered Updates regarding the use of glucose-lowering agents are discussed from a clinical point of view. Some new viewpoints concern older antidiabetic agents such as metformin, sulfonylureas and glitazones whose benefit-risk balance has been revisited, especially in high risk patients...
September 7, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28865058/combined-metformin-associated-lactic-acidosis-and-euglycemic-ketoacidosis
#6
Verena Schwetz, Florian Eisner, Gernot Schilcher, Kathrin Eller, Johannes Plank, Alice Lind, Thomas R Pieber, Julia K Mader, Philipp Eller
BACKGROUND: In renal failure metformin can lead to lactic acidosis. Additional inhibition of hepatic gluconeogenesis by accumulation of the drug may aggravate fasting-induced ketoacidosis. We report the occurrence of metformin-associated lactic acidosis (MALA) with concurrent euglycemic ketoacidosis (MALKA) in three patients with renal failure. CASE PRESENTATIONS: Patient 1: a 78-year-old woman (pH = 6.89, lactic acid 22 mmol/l, serum ketoacids 7.4 mmol/l and blood glucose 63 mg/dl) on metformin and insulin treatment...
September 1, 2017: Wiener Klinische Wochenschrift
https://www.readbyqxmd.com/read/28856166/ketoacidosis-with-canagliflozin-prescribed-for-phosphoinositide-3-kinase-inhibitor-induced-hyperglycemia-a-case-report
#7
Christopher Bowman, Vandana Abramson, Melissa Wellons
Context. Many phosphoinositide-3-kinase (PI3K) inhibitors are under trial for cancer treatment. We present a patient taking taselisib who developed ketoacidosis within 1 week of starting canagliflozin. Case Description. A 69-year-old female patient with no previous history of diabetes mellitus was enrolled in a clinical trial for taselisib therapy in stage IV breast cancer. Hyperglycemia treatment with metformin was insufficient and not tolerated. The addition of canagliflozin daily resulted in ketoacidosis and hospitalization within 1 week...
July 2017: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/28846182/effects-of-sodium-glucose-co-transporter-2-sglt2-inhibitors-on-serum-uric-acid-level-a-meta-analysis-of-randomized-controlled-trials
#8
Yumo Zhao, Lubin Xu, Dongli Tian, Peng Xia, Hua Zheng, Li Wang, Limeng Chen
To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM), PubMed, CENTRAL, EMBASE, and ClinicalTrials.gov were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to 20 May 2017. Sixty-two studies totaling 34,941 patients were included. Either SGLT2 inhibitor (empagliflozin, canagliflozin, dapagliflozin, tofogliflozin, luseogliflozin or ipragliflozin) significantly decreased SUA levels compared with control (total WMD -37...
August 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28837785/canagliflozin-prevents-scopolamine-induced-memory-impairment-in-rats-comparison-with-galantamine-hydrobromide-action
#9
Nadia M S Arafa, Elham H A Ali, Mohamed Kamel Hassan
Canagliflozin (CAN) is a sodium-glucose co-transporter 2 (SGLT2) inhibitor indicated to improve glycemic control in adults with type 2 diabetes mellitus. There is a little information about its effect on the cholinergic system that proposed mechanism for memory improvement occurring by SGLT2 drugs. This study aimed to estimate the effect of CAN as compared to galantamine (GAL) treatments for two weeks on scopolamine hydrobromide (SCO) -induced memory dysfunction in experimental rats. Animals divided into six groups; control (CON), CAN, GAL, SCO, SCO + CAN and SCO + GAL...
August 21, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28837279/-cardiorenal-protection-with-sglt2-inhibitors-gliflozins-from-empa-reg-outcome-to-canvas
#10
André J Scheen, Philippe Ernest, Bernard Jandrain
The cardiovascular (CV) and renal protection reported with empagliflozin in EMPA-REG OUTCOME is now confirmed with canagliflozin in CANVAS in patients with type 2 diabetes and high cardiovascular risk: similar and significant reductions in major CV events (-14 vs. -14%), in hospitalisations for heart failure (-35 vs. -33%) and in renal events (-39 vs. -40%). The greater reduction in CV mortality (-38 vs. - 13%) and all-cause mortality (-32 vs. -13%) in EMPA-REG OUTCOME than in CANVAS may be explained by the greater proportion of patients with CV disease (secondary prevention : 99 vs...
August 23, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28836175/canagliflozin-a-review-in-type-2-diabetes
#11
Emma D Deeks, André J Scheen
Canagliflozin (Invokana(®)) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated in various countries worldwide for the once-daily oral treatment of type 2 diabetes (T2D). Canagliflozin lowers blood glucose levels independently of insulin, with the inhibition of SGLT2 reducing renal reabsorption of glucose and increasing excretion of glucose in the urine. In well-designed clinical trials, canagliflozin (as first-line monotherapy or add-on therapy to other antihyperglycaemic agents) improved glycaemic control in adults with T2D, including those of older age and/or at high cardiovascular (CV) risk, and also had beneficial effects on their bodyweight and blood pressure (BP)...
August 23, 2017: Drugs
https://www.readbyqxmd.com/read/28833358/syntheses-of-isotope-labeled-sglt2-inhibitor-canagliflozin-jnj-28431754
#12
Ronghui Lin, David C Hoerr, Larry E Weaner, Rhys Salter
Canagliflozin (Invokana®, JNJ-28431754) is an orally bioavailable and selective SGLT2 (subtype 2 sodium-glucose transport protein) inhibitor approved for the treatment of type 2 diabetes. Herein we report the synthesis of (13) C and (14) C-labeled canagliflozin. Stable isotope-labeled [(13) C6 ]canagliflozin was synthesized in four steps starting from [(13) C6 ]-labeled glucose. [(14) C]-Labeled canagliflozin was synthesized by incorporation of [(14) C] into the benzylic position between the thiophene and benzene rings of the compound...
August 18, 2017: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/28829209/the-effect-of-sglt2-inhibitors-on-cardiovascular-events-and-renal-function
#13
Konstantinos P Imprialos, Konstantinos Stavropoulos, Michael Doumas, Asterios Karagiannis, Vasilios G Athyros
Sodium-glucose co-transporters-2inhibitors have emerged as a very promising antidiabetic drug class, with data from the two available cardiovascular trials of this class suggesting remarkable benefits in terms of cardiovascular events, total mortality and renal outcomes. Areas covered: Data point toward clinically meaningful benefits from SGLT-2inhibition on a variety of cardiovascular risk factors. Empagliflozin, and to a lesser extent canagliflozin, resulted in significant reductions of an abundance of cardiovascular mortality and morbidity endpoints...
August 28, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28827404/acute-kidney-injury-in-patients-on-sglt2-inhibitors-a-propensity-matched-analysis
#14
Girish N Nadkarni, Rocco Ferrandino, Alexander Chang, Aditya Surapaneni, Kinsuk Chauhan, Priti Poojary, Aparna Saha, Bart Ferket, Morgan E Grams, Steven G Coca
OBJECTIVE: Sodium-glucose cotransporter-2 (SGLT2) inhibitors are new medications that improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). However, the Food and Drug Administration has issued alerts regarding increased acute kidney injury (AKI) risk with canagliflozin and dapagliflozin. We aimed to assess the real-world risk of AKI in new SGLT2 inhibitor users in two large health care utilization cohorts of patients with T2D. RESEARCH DESIGN AND METHODS: We used longitudinal data from the Mount Sinai chronic kidney disease registry and the Geisinger Health System cohort...
August 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28826578/sglt2-inhibitors-induced-electrolyte-abnormalities-an-analysis-of-the-associated-mechanisms
#15
REVIEW
T D Filippatos, V Tsimihodimos, G Liamis, M S Elisaf
AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that affect serum electrolytes levels. The aim of this review is the detailed presentation of the associated mechanisms of the SGLT2 inhibitors-induced electrolyte abnormalities. MATERIALS AND METHODS: Eligible trials and relevant articles published in PubMed (last search in July 2017) are included in the review. RESULTS: SGLT2 inhibitors induce small increases in serum concentrations of magnesium, potassium and phosphate...
August 11, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28822714/cardiovascular-disease-leads-to-a-new-algorithm-for-diabetes-treatment
#16
REVIEW
Valentina Rodriguez, Matthew C Weiss, Howard Weintraub, Ira J Goldberg, Arthur Schwartzbard
Patients with diabetes mellitus have increased rates of atherosclerotic cardiovascular disease (CVD) and heart failure (HF). This increase occurs despite optimal lipid-lowering therapies. We reviewed clinical trials of diabetes treatments and their effects on circulating plasma lipoproteins and CVD. Several earlier studies failed to demonstrate clear CVD benefit from diabetes therapies. In addition, triglyceride-reducing agents did not reduce overall CVD in large clinical trials although these trials were not conducted in cohorts selected as hypertriglyceridemic...
July 22, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28814245/benefits-of-sglt2-inhibitors-beyond-glycemic-control-a-focus-on-metabolic-cardiovascular-and-renal-outcomes
#17
Molly G Minze, Kayley Will, Brian T Terrell, Robin L Black, Brian K Irons
BACKGROUND: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new pharmacotherapeutic class for the treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE: To evaluate beneficial effects of the SGLT2 inhibitors on metabolic, cardiovascular, and renal outcomes. METHODS: A Pub-Med search (1966 to July 2017) was performed of published English articles using keywords sodium-glucose co-transporter 2 inhibitors, canagliflozin, dapagliflozin, and empagliflozin...
August 16, 2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28812381/retrospective-review-of-sglt2-inhibitor-exposures-reported-to-13-poison-centers
#18
Scott E Schaeffer, Carol DesLauriers, Henry A Spiller, Alfred Aleguas, Salvador Baeza, Mark L Ryan
BACKGROUND: SGLT2 inhibitors are a new class of oral antidiabetics prescribed in the United States since 2013. They act by inhibiting reabsorption of glucose in the proximal convoluted tubule of the kidney, allowing excess glucose to be excreted. Little has been reported regarding effects of non-therapeutic exposure to this class of medication. METHODS: Retrospective records from 13 poison centers were examined for human exposures to SGLT2 inhibitors between 1st January 2013 and 31st December 2016...
August 16, 2017: Clinical Toxicology
https://www.readbyqxmd.com/read/28811856/serum-betatrophin-levels-and-clinical-features-in-patients-with-poorly-controlled-type-2-diabetes
#19
Kohzo Takebayashi, Kenji Hara, Tomoko Terasawa, Rika Naruse, Mariko Suetsugu, Takafumi Tsuchiya, Toshihiko Inukai
BACKGROUND: Betatrophin is a hormone mainly secreted by the liver that influences lipid metabolisms. The main purposes of this study were to investigate the effect of canagliflozin (a sodium glucose transporter 2 inhibitor) on circulating betatrophin levels, and to investigate the correlation of various markers associated with glucose and lipid metabolisms with betatrophin in patients with poorly controlled type 2 diabetes. METHODS: Patients were randomly divided into a control group (n = 15) and a canagliflozin-treated group (n = 15)...
September 2017: Journal of Clinical Medicine Research
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
#20
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
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