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Dapagliflozin and canagliflozin

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https://www.readbyqxmd.com/read/27867961/cardio-renal-protection-with-empagliflozin
#1
Richard J MacIsaac, George Jerums, Elif I Ekinci
Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27862830/urinary-tract-and-genital-infections-in-patients-with-type-2-diabetes-treated-with-sodium-glucose-cotransporter-2-inhibitors-a-meta-analysis-of-randomized-controlled-trials
#2
Dandan Li, Tiansheng Wang, Su Shen, Zhenwei Fang, Yue Dong, Huilin Tang
AIMS: Sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with increased risk of urinary tract infections (UTIs) and genital infections. However, differences among different doses were still controversial. Thus, we aimed to evaluate effects of different SGLT2 inhibitors on the risk of UTIs and genital infections in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We systematically searched PubMed, Embase, CENTRAL, and ClinicalTrials...
November 12, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27835680/benefits-and-harms-of-sodium-glucose-co-transporter-2-inhibitors-in-patients-with-type-2-diabetes-a-systematic-review-and-meta-analysis
#3
Heidi Storgaard, Lise L Gluud, Cathy Bennett, Magnus F Grøndahl, Mikkel B Christensen, Filip K Knop, Tina Vilsbøll
OBJECTIVE: Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) are a novel drug class for the treatment of diabetes. We aimed at describing the maximal benefits and risks associated with SGLT2-i for patients with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND STUDY SELECTION: We included double-blinded, randomised controlled trials (RCTs) evaluating SGLT2-i administered in the highest approved therapeutic doses (canagliflozin 300 mg/day, dapagliflozin 10 mg/day, and empagliflozin 25 mg/day) for ≥12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27826881/bone-fractures-with-sodium-glucose-co-transporter-2-inhibitors-how-real-is-the-risk
#4
REVIEW
Edoardo Mannucci, Matteo Monami
This article succinctly summarizes the available evidence on the risk of bone fractures with sodium-glucose co-transporter-2 inhibitors. The US Food and Drug Administration has strengthened the warning for canagliflozin related to the increased risk of bone fractures, and added new information about decreased bone mineral density. The agency has also said that it will evaluate the risk of bone fractures with other drugs in the sodium-glucose co-transporter-2 inhibitor class. Increases in parathyroid hormone levels and decreases in 1,25-dihydroxyvitamin D levels have been postulated as possible mechanisms...
November 8, 2016: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/27822054/impact-of-sodium-glucose-cotransporter-2-inhibitors-on-blood-pressure
#5
REVIEW
James W Reed
SGLT2 inhibitors are glucose-lowering agents used to treat type 2 diabetes mellitus (T2DM). These agents target the kidney to promote urinary glucose excretion, resulting in improved blood glucose control. SGLT2-inhibitor therapy is also associated with weight loss and blood pressure (BP) lowering. Hypertension is a common comorbidity in patients with T2DM, and is associated with excess morbidity and mortality. This review summarizes data on the effect of SGLT2 inhibitors marketed in the US (namely canagliflozin, dapagliflozin, or empagliflozin) on BP in patients with T2DM...
2016: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/27689018/the-diabetes-medication-canagliflozin-reduces-cancer-cell-proliferation-by-inhibiting-mitochondrial-complex-i-supported-respiration
#6
Linda A Villani, Brennan K Smith, Katarina Marcinko, Rebecca J Ford, Lindsay A Broadfield, Alex E Green, Vanessa P Houde, Paola Muti, Theodoros Tsakiridis, Gregory R Steinberg
OBJECTIVE: The sodium-glucose transporter 2 (SGLT2) inhibitors Canagliflozin and Dapagliflozin are recently approved medications for type 2 diabetes. Recent studies indicate that SGLT2 inhibitors may inhibit the growth of some cancer cells but the mechanism(s) remain unclear. METHODS: Cellular proliferation and clonogenic survival were used to assess the sensitivity of prostate and lung cancer cell growth to the SGLT2 inhibitors. Oxygen consumption, extracellular acidification rate, cellular ATP, glucose uptake, lipogenesis, and phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase, and the p70S6 kinase were assessed...
October 2016: Molecular Metabolism
https://www.readbyqxmd.com/read/27666177/meta-analysis-of-effects-of-sodium-glucose-cotransporter-2-inhibitors-on-cardiovascular-outcomes-and-all-cause-mortality-among-patients-with-type-2-diabetes-mellitus
#7
Huilin Tang, Zhenwei Fang, Tiansheng Wang, Wei Cui, Suodi Zhai, Yiqing Song
The benefit or risk of sodium glucose cotransporter 2 (SGLT2) inhibitors on cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus has not been established. We aimed to assess the comparative CV safety and mortality risk associated with the use of SGLT2 inhibitors. PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were systematically searched up to January 27, 2016, to identify randomized controlled trials (RCTs) with the use of SGLT2 inhibitors of at least 24 weeks of duration...
August 31, 2016: American Journal of Cardiology
https://www.readbyqxmd.com/read/27648101/closing-the-knowledge-gap-on-cardiovascular-disease-in-type-2-diabetes-the-empa-reg-outcome-trial-and-beyond
#8
REVIEW
Elif A Oral
Type 2 diabetes mellitus (T2DM) is associated with marked cardiovascular (CV) morbidity and mortality, including heart failure (HF). Until recently, an oral glucose-lowering agent that improved hyperglycemia as well as provided CV benefits in patients with T2DM and cardiovascular disease (CVD) was lacking. The newest class of glucose-lowering agents, sodium glucose cotransporter 2 (SGLT2) inhibitors, includes canagliflozin, dapagliflozin, and empagliflozin. Prior to the release of the LEADER trial results, the recent EMPA-REG OUTCOME study was the only dedicated CV trial to demonstrate a reduction in major adverse cardiac events, CV mortality, and all-cause mortality and a reduction in hospitalization for HF with empagliflozin, given on top of standard-of-care therapy in patients with T2DM and CVD...
2016: Drugs in Context
https://www.readbyqxmd.com/read/27628105/elevated-serum-magnesium-associated-with-sglt2-inhibitor-use-in-type-2-diabetes-patients-a-meta-analysis-of-randomised-controlled-trials
#9
Huilin Tang, Xi Zhang, Jingjing Zhang, Yufeng Li, Liana C Del Gobbo, Suodi Zhai, Yiqing Song
AIMS/HYPOTHESIS: By analysing available evidence from randomised controlled trials (RCTs), we aimed to examine whether and to what extent sodium-glucose cotransporter 2 (SGLT2) inhibitors affect serum electrolyte levels in type 2 diabetes patients. METHODS: We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) and ClinicalTrials.gov up to 24 May 2016 for published RCTs of SGLT2 inhibitors that reported changes in serum electrolyte levels...
December 2016: Diabetologia
https://www.readbyqxmd.com/read/27620988/dapagliflozin-binds-specifically-to-sodium-glucose-cotransporter-2-in-the-proximal-renal-tubule
#10
Chiara Ghezzi, Amy S Yu, Bruce A Hirayama, Vladimir Kepe, Jie Liu, Claudio Scafoglio, David R Powell, Sung-Cheng Huang, Nagichettiar Satyamurthy, Jorge R Barrio, Ernest M Wright
Kidneys contribute to glucose homeostasis by reabsorbing filtered glucose in the proximal tubules via sodium-glucose cotransporters (SGLTs). Reabsorption is primarily handled by SGLT2, and SGLT2-specific inhibitors, including dapagliflozin, canagliflozin, and empagliflozin, increase glucose excretion and lower blood glucose levels. To resolve unanswered questions about these inhibitors, we developed a novel approach to map the distribution of functional SGLT2 proteins in rodents using positron emission tomography with 4-[(18)F]fluoro-dapagliflozin (F-Dapa)...
September 12, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27604638/physiologically-based-pharmacokinetic-pharmacodynamic-modeling-to-predict-concentrations-and-actions-of-sodium-dependent-glucose-transporter-2-inhibitor-canagliflozin-in-human-intestines-and-renal-tubules
#11
Kazumi Mori, Ryuta Saito, Yoshinobu Nakamaru, Makiko Shimizu, Hiroshi Yamazaki
Canagliflozin is a recently developed sodium-glucose cotransporter (SGLT) 2 inhibitor that promotes renal glucose excretion and is considered to inhibit renal SGLT2 from the luminal side of proximal tubules. Canagliflozin reportedly inhibits SGLT1 weakly and suppresses postprandial plasma glucose, suggesting that it also inhibits intestinal SGLT1. However, it is difficult to measure the drug concentrations of these assumed sites of action directly. The pharmacokinetic-pharmacodynamic (PK/PD) relationships of canagliflozin remain poorly characterized...
September 7, 2016: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/27541294/sglt2-inhibitors-benefit-risk-balance
#12
REVIEW
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
https://www.readbyqxmd.com/read/27535028/effects-of-antidiabetic-drugs-on-the-incidence-of-macrovascular-complications-and-mortality-in-type-2-diabetes-mellitus-a-new-perspective-on-sodium-glucose-co-transporter-2-inhibitors
#13
Dario Rahelić, Eugen Javor, Tomo Lucijanić, Marko Skelin
Elevated haemoglobin A1c (HbA1c) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence, regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear...
August 18, 2016: Annals of Medicine
https://www.readbyqxmd.com/read/27488726/effects-of-sglt-2-inhibitors-on-mortality-and-cardiovascular-events-a-comprehensive-meta-analysis-of-randomized-controlled-trials
#14
Matteo Monami, Ilaria Dicembrini, Edoardo Mannucci
AIMS: EMPAREG OUTCOME study showed a reduction in cardiovascular events in patients treated with the sodium-glucose transporter 2 inhibitor (SGLT2i) empagliflozin, as compared to placebo. Other drugs of the same class are currently been investigated for cardiovascular outcomes. In the meanwhile, a re-analysis of data collected in available studies can add relevant insight. METHODS: A MEDLINE search for SGLT-2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials up to November 16, 2015...
August 4, 2016: Acta Diabetologica
https://www.readbyqxmd.com/read/27471597/the-dka-that-wasn-t-a-case-of-euglycemic-diabetic-ketoacidosis-due-to-empagliflozin
#15
Nellowe Candelario, Jedrzej Wykretowicz
Sodium glucose co-transporter (SGLT-2) inhibitor is a relatively new medication used to treat diabetes. At present, the Food and Drug Administration (FDA) has only approved three medications (canagliflozin, dapagliflozin and empagliflozin) in this drug class for the management of Type 2 diabetes. In May 2015, the FDA issued a warning of ketoacidosis with use of this drug class. Risk factors for the development of ketoacidosis among patients who take SGLT-2 inhibitors include decrease carbohydrate intake/starvation, acute illness and decrease in insulin dose...
July 2016: Oxford Medical Case Reports
https://www.readbyqxmd.com/read/27470878/sodium-glucose-cotransporter-2-inhibitors-in-the-treatment-of-diabetes-mellitus-cardiovascular-and-kidney-effects-potential-mechanisms-and-clinical-applications
#16
Hiddo J L Heerspink, Bruce A Perkins, David H Fitchett, Mansoor Husain, David Z I Cherney
Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures by 4 to 6 and 1 to 2 mm Hg, respectively, which may underlie cardiovascular and kidney benefits...
September 6, 2016: Circulation
https://www.readbyqxmd.com/read/27430987/characterization-and-comparison-of-sodium-glucose-cotransporter-2-inhibitors-part-2-antidiabetic-effects-in-type-2-diabetic-mice
#17
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
Previously we investigated the pharmacokinetic, pharmacodynamic, and pharmacologic properties of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan using normal and diabetic mice. We classified the SGLT2 inhibitors with respect to duration of action as either long-acting (ipragliflozin and dapagliflozin) or intermediate-acting (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin). In the present study, antidiabetic effects of repeated administration of these SGLT2 inhibitors in type 2 diabetic mice were investigated...
July 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27417322/%C3%A2-empagliflozin-diabetes-and-outcomes
#18
(no author information available yet)
The prevalence of type 2 diabetes is rising, and in 2015 more than 5% of adults in the UK were affected by this condition.(1,2) Management of type 2 diabetes includes encouraging lifestyle changes (increased exercise, modification of diet and smoking cessation) alongside the provision of medication to minimise long-term complications and manage blood sugar control while avoiding unwanted effects of drug treatment.(3) Of particular importance, people with type 2 diabetes are at increased risk of cardiovascular disease, and therefore the aims of treatment also include modification of associated risk factors...
July 2016: Drug and Therapeutics Bulletin
https://www.readbyqxmd.com/read/27407013/lack-of-evidence-for-a-harmful-effect-of-sodium-glucose-co-transporter-2-sglt2-inhibitors-on-fracture-risk-among-type-2-diabetes-patients-a-network-and-cumulative-meta-analysis-of-randomized-controlled-trials
#19
H L Tang, D D Li, J J Zhang, Y H Hsu, T S Wang, S D Zhai, Y Q Song
AIM: To evaluate the comparative effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on risk of bone fracture in patients with type 2 diabetes mellitus (T2DM). METHODS: PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were systematically searched from inception to 27 January 2016 to identify randomized controlled trials (RCTs) reporting the outcome of fracture in patients with T2DM treated with SGLT2 inhibitors. Pairwise and network meta-analyses, as well as a cumulative meta-analysis, were performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs)...
December 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27382338/the-treatment-of-type-2-diabetes-in-the-presence-of-renal-impairment-what-we-should-know-about-newer-therapies
#20
REVIEW
Melanie Davies, Sudesna Chatterjee, Kamlesh Khunti
Worldwide, an estimated 200 million people have chronic kidney disease (CKD), the most common causes of which include hypertension, arteriosclerosis, and diabetes. Importantly, ~40% of patients with diabetes develop CKD, yet evidence from major multicenter randomized controlled trials shows that intensive blood glucose control through pharmacological intervention can reduce the incidence and progression of CKD. Standard therapies for the treatment of type 2 diabetes include metformin, sulfonylureas, meglitinides, thiazolidinediones, and insulin...
2016: Clinical Pharmacology: Advances and Applications
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