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Dapagliflozin

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https://www.readbyqxmd.com/read/27908315/-life-threatening-ketoacidosis-in-a-25-year-old-woman-treated-with-sodium-glucose-cotransporter-2-inhibitor
#1
Mats Jacob Hermansson Lindberg, Frans Brandt Kristensen, Alev Yildiz
We report a case of atypical ketoacidosis in a patient treated with a sodium-glucose cotransporter- (SGLT) 2 inhibitor. The 25-year-old woman, who one year earlier had been prescribed dapagliflozin for presumed Type 2 diabetes, came to the emergency department in a state of severe ketoacidosis, pH 6.85, and a plasma glucose level of 14.3 mmol/l. She received standard treatment and recovered. We discuss the increasing evidence for atypical ketoacidosis being a serious side effect of the SGLT2 inhibitors.
November 21, 2016: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/27868223/synthesis-of-unlabelled-and-stable-isotope-labelled-glucuronide-metabolites-of-dapagliflozin-and-synthesis-of-stable-isotope-labelled-dapagliflozin
#2
Kai Cao, John A Brailsford, Ming Yao, Janet Caceres-Cortes, Robert Espina, Samuel J Bonacorsi
Two regioisomeric glucuronide metabolites of dapagliflozin (BMS-512148) were synthesized and used to elucidate the structures of dapagliflozin metabolites observed in human urine samples. The structures of the synthetic metabolites were assigned by HMBC, ROESY, and TOCSY experiments. Analogues of these metabolites containing carbon-13 as a stable-label were also prepared for use as internal standards for the analysis of urine samples obtained from patients participating in clinical studies. This article is protected by copyright...
November 21, 2016: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/27867961/cardio-renal-protection-with-empagliflozin
#3
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/27866027/cardiovascular-outcomes-with-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-type-ii-diabetes-mellitus-a-meta-analysis-of-placebo-controlled-randomized-trials
#4
Marwan Saad, Ahmed N Mahmoud, Islam Y Elgendy, Ahmed Abuzaid, Amr F Barakat, Akram Y Elgendy, Mohammad Al-Ani, Amgad Mentias, Ramez Nairooz, Anthony A Bavry, Debabrata Mukherjee
BACKGROUND: The impact of sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiovascular outcomes in patients with type II diabetes mellitus (DM) is not well established. METHODS: We searched electronic databases from inception through July 2016 for randomized, placebo-controlled trials, involving SGLT-2 inhibitors. Fixed-effects summary odds ratios (OR) were constructed using Peto model. RESULTS: Eighty-one trials with a total of 37,195 patients were included...
November 9, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27865300/effect-of-dapagliflozin-treatment-on-fluid-and-electrolyte-balance-in-diabetic-rats
#5
Ling Chen, Lauren M LaRocque, Orhan Efe, Juan Wang, Jeff M Sands, Janet D Klein
AIM: This study evaluates the effect of dapagliflozin, a SGLT2 inhibitor, on fluid or electrolyte balance and its effect on urea transporter-A1 (UT-A1), aquaporin-2 (AQP2) and Na-K-2Cl cotransporter (NKCC2) protein abundance in diabetic rats. METHODS: Diabetes mellitus (DM) was induced by injection of streptozotocin into the tail vein. Serum Na(+), K(+), Cl(-) concentration, urine Na(+), K(+), Cl(-) excretion, blood glucose, urine glucose excretion, urine volume, urine osmolality and urine urea excretion were analyzed after the administration of dapagliflozin...
November 2016: American Journal of the Medical Sciences
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
#6
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/27849380/combined-treatment-with-saxagliptin-plus-dapagliflozin-reduces-insulin-levels-by-increased-insulin-clearance-and-improves-%C3%AE-cell-function
#7
Ella Ekholm, Lars Hansen, Eva Johnsson, Nayyar Iqbal, Björn Carlsson, Hungta Chen, Boaz Hirshberg
OBJECTIVE: To determine if reduction in serum insulin with dapagliflozin plus saxagliptin or dapagliflozin add-on to metformin contributed to increased insulin clearance and to assess the effects of these treatments on β-cell function. METHODS: Patients (A1C 8.0%-12.0%) were randomized to 24-week, double-blind treatment with saxagliptin 5 mg/d plus dapagliflozin 10 mg/d (n=179), saxagliptin 5 mg/d plus placebo (n=176), or dapagliflozin 10 mg/d plus placebo (n=179) added to metformin...
November 16, 2016: Endocrine Practice
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
#8
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/27829948/increased-hematocrit-during-sodium-glucose-cotransporter-2-inhibitor-therapy-indicates-recovery-of-tubulointerstitial-function-in-diabetic-kidneys
#9
REVIEW
Motoaki Sano, Makoto Takei, Yasuyuki Shiraishi, Yoshihiko Suzuki
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been attracting attention for cardiovascular as well as antidiabetic effects since the results of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME Trial) were reported. The hematocrit increases during treatment with SGLT2 inhibitors, which have a diuretic effect but do not cause sufficient hemoconcentration to increase the risk of cerebral infarction. Elevation of the hematocrit during SGLT2 inhibitor therapy is presumed to involve enhancement of erythropoiesis in addition to hemoconcentration...
December 2016: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/27826881/bone-fractures-with-sodium-glucose-co-transporter-2-inhibitors-how-real-is-the-risk
#10
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/27822077/changes-in-hba1c-body-weight-and-systolic-blood-pressure-in-type-2-diabetes-patients-initiating-dapagliflozin-therapy-a-primary-care-database-study
#11
Markus F Scheerer, Roland Rist, Orm Proske, Annika Meng, Karel Kostev
AIMS: To investigate changes in glycated hemoglobin (HbA1c), body weight (BW), and systolic blood pressure (SBP) in type 2 diabetes (T2D) primary care patients initiating dapagliflozin treatment. METHODS: T2D patients who started dapagliflozin in 985 general and 32 diabetologist practices (Disease Analyzer, Germany: December 2012-October 2014) were analyzed (3- and 6-month follow-up). Multivariate linear regression analyses were used to identify clinical characteristics and comorbidity associated with changes in HbA1c, BW, and SBP...
2016: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/27822054/impact-of-sodium-glucose-cotransporter-2-inhibitors-on-blood-pressure
#12
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/27817216/cost-effectiveness-analysis-of-dapagliflozin-versus-glimepiride-as-monotherapy-in-chinese-population-with-type-2-diabetes-mellitus
#13
Hui Shao, Suodi Zhai, Dajin Zou, Mohammed Umer Mir, Nadine K Zawadzki, Qian Shi, Shuqian Liu, Lizheng Shi
OBJECTIVE: To evaluate the long-term cost-effectiveness of dapagliflozin (a novel sodium-glucose co-transporter -2 inhibitor) versus glimepiride (a widely used sulfonylurea), when applied as monotherapy in patients with type 2 diabetes mellitus (T2DM) in China. METHODS: Literature screening, meta-analysis and indirect comparison were used to evaluate the efficacy and safety between dapagliflozin and glimepiride. Direct medication costs and medical expenditure on treating diabetes related comorbidities were calculated based on published and local source and reported in 2015 Chinese Renminbi (RMB)...
November 5, 2016: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/27806087/cost-effectiveness-of-dapagliflozin-versus-acarbose-as-a-monotherapy-in-type-2-diabetes-in-china
#14
Shuyan Gu, Yiming Mu, Suodi Zhai, Yuhang Zeng, Xuemei Zhen, Hengjin Dong
OBJECTIVE: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China. METHODS: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs...
2016: PloS One
https://www.readbyqxmd.com/read/27802313/effect-of-sodium-glucose-co-transporter-2-inhibitor-dapagliflozin-on-renal-renin-angiotensin-system-in-an-animal-model-of-type-2-diabetes
#15
Seok Joon Shin, Sungjin Chung, Soo Jung Kim, Eun-Mi Lee, Young-Hye Yoo, Ji-Won Kim, Yu-Bae Ahn, Eun-Sook Kim, Sung-Dae Moon, Myung-Jun Kim, Seung-Hyun Ko
BACKGROUND: Renal renin-angiotensin system (RAS) activation is one of the important pathogenic mechanisms in the development of diabetic nephropathy in type 2 diabetes. The aim of this study was to investigate the effects of a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, dapagliflozin, on renal RAS in an animal model with type 2 diabetes. METHODS: Dapagliflozin (1.0 mg/kg, OL-DA) or voglibose (0.6 mg/kg, OL-VO, diabetic control) (n = 10 each) was administered to Otsuka Long-Evans Tokushima Fatty (OLETF) rats for 12 weeks...
2016: PloS One
https://www.readbyqxmd.com/read/27790048/quality-measure-attainment-with-dapagliflozin-plus-metformin-extended-release-as-initial-combination-therapy-in-patients-with-type-2-diabetes-a-post-hoc-pooled-analysis-of-two-clinical-studies
#16
Kelly F Bell, Arie Katz, John J Sheehan
BACKGROUND: The use of quality measures attempts to improve safety and health outcomes and to reduce costs. In two Phase III trials in treatment-naive patients with type 2 diabetes, dapagliflozin 5 or 10 mg/d as initial combination therapy with metformin extended-release (XR) significantly reduced glycated hemoglobin (A1C) from baseline to 24 weeks and allowed higher proportions of patients to achieve A1C <7% vs dapagliflozin or metformin monotherapy. OBJECTIVE: A pooled analysis of data from these two studies assessed the effect of dapagliflozin 5 or 10 mg/d plus metformin XR (combination therapy) compared with placebo plus metformin XR (metformin monotherapy) on diabetes quality measures...
2016: Risk Management and Healthcare Policy
https://www.readbyqxmd.com/read/27761881/clinical-effectiveness-and-impact-on-insulin-therapy-cost-after-addition-of-dapagliflozin-to-patients-with-uncontrolled-type-2-diabetes
#17
Bhavana Sosale, Aravind Sosale, Arpandev Bhattacharyya
INTRODUCTION: Dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, is a promising drug approved for the treatment of type 2 diabetes mellitus (T2DM). However, its cost is an obstacle for use in developing countries like India. Thus, we aimed to analyse the impact on the cost of insulin therapy after adding dapagliflozin for patients using insulin in real-world clinical practice. METHODS: This retrospective chart review study included patients with uncontrolled T2DM previously on maximum doses of OADs and insulin therapy, initiated on dapagliflozin...
December 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27754289/br-08-1-high-sodium-intake-reduction-in-diabetes-with-hypertension
#18
Zhiming Zhu
Management of hypertension in diabetes is critical for reducing cardiovascular mortality and morbidity. Dietary approaches for controlling high blood pressure have historically focused on sodium. Thus, many guidelines recommend that patients with type 2 diabetes reduce high sodium intake. Nonetheless, the potential benefits of sodium reduction are debatable. The kidney has a crucial role in glucose filtration and reabsorption in addition to its regulation of fluid and electrolyte homeostasis. A key factor linking sodium uptake and glucose transport is the sodium-glucose cotransporter 2 (SGLT2) in renal proximal tubular cells...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753976/os-12-03-sglt-2-inhibition-with-dapagliflozin-reduces-tissue-sodium-content
#19
Roland Schmieder, Christian Ott, Peter Linz, Agnes Jumar, Stefanie Friedrich, Jens Titze, Matthias Hammon, Michael Uder, Iris Kistner
OBJECTIVE: Sodium tissue content by Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and, in parallel, of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes leads to decreased tissue sodium content due to its pharmacological action. DESIGN AND METHOD: In a prospective, double blind, placebo controlled, cross-over trial 59 patients (61 ± 7...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27738639/influence-of-dapagliflozin-on-glycemic-variations-in-patients-with-newly-diagnosed-type-2-diabetes-mellitus
#20
Feng-Fei Li, Gu Gao, Qian Li, Hong-Hong Zhu, Xiao-Fei Su, Jin-Dan Wu, Lei Ye, Jian-Hua Ma
Objectives. To observe changes in blood glycemic variations and oxidative stress level before and after dapagliflozin treatment in patients with newly diagnosed T2DM. Methods. This was a randomized, double-blind, placebo-controlled, phase 3 trial. A total of 28 patients with newly diagnosed T2DM with HbA1c levels of 7.5-10.5% were randomly selected to receive dapagliflozin or placebo treatment for 24 weeks. After baseline data were collected, we analyzed glycemic variations and plasma 8-iso PGF2α level at baseline and at the endpoint...
2016: Journal of Diabetes Research
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