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Sodium glucose transport inhibitors

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https://www.readbyqxmd.com/read/28332143/the-relationship-between-increases-in-morning-spot-urinary-glucose-excretion-and-decreases-in-hba1c-in-patients-with-type-2-diabetes-after-taking-an-sglt2-inhibitor-a-retrospective-longitudinal-study
#1
So Ra Kim, Yong-Ho Lee, Eun Seok Kang, Bong-Soo Cha, Byung-Wan Lee
INTRODUCTION: Sodium glucose co-transporter 2 (SGLT2) inhibitors increase urinary glucose excretion (UGE) by reducing the renal threshold for glucose excretion, which results in decreased serum glucose concentrations in patients with type 2 diabetes mellitus (T2D). However, no study to date has determined whether larger increases in UGE after SGLT2 inhibitor treatment correspond to larger reductions in glycated hemoglobin (HbA1C). METHODS: We enrolled participants who were newly prescribed an SGLT2 inhibitor (dapagliflozin 10 mg or ipragliflozin 50 mg, once daily) as an add-on therapy...
March 22, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28327140/efficacy-and-safety-of-canagliflozin-in-patients-with-type-2-diabetes-based-on-history-of-cardiovascular-disease-or-cardiovascular-risk-factors-a-post-hoc-analysis-of-pooled-data
#2
Michael J Davies, Katherine Merton, Ujjwala Vijapurkar, Jacqueline Yee, Rong Qiu
BACKGROUND: Treatment of patients with type 2 diabetes mellitus (T2DM) and a history of cardiovascular (CV) disease or CV risk factors may present clinical challenges due to the presence of comorbid conditions and the use of concomitant medications. The sodium glucose co-transporter 2 inhibitor, canagliflozin, has been shown to improve glycaemic control and reduce body weight and blood pressure (BP) with a favourable tolerability profile in a broad range of patients with T2DM. This post hoc analysis assessed the efficacy and safety of canagliflozin in patients with T2DM based on CV disease history or CV risk factors...
March 21, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28324484/sodium-glucose-co-transporter-2-sglt2-inhibitor-comparing-trial-data-and-real-world-use
#3
Andrew McGovern, Michael Feher, Neil Munro, Simon de Lusignan
INTRODUCTION: The first cardiovascular safety trial in the sodium-glucose co-transporter-2 (SGLT2) inhibitor drug class, the Empagliflozin Cardiovascular Outcomes and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial, demonstrated significant cardiovascular risk reduction with empagliflozin. It is currently not clear what proportions of people with type 2 diabetes (T2DM) have the same high cardiovascular risk as those included in the trial, and will therefore be likely to experience the same cardiovascular benefit...
March 21, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#4
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFA) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
February 21, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323512/evaluating-the-costs-of-glycemic-response-with-canagliflozin-versus-dapagliflozin-and-empagliflozin-as-add-on-to-metformin-in-patients-with-type-2-diabetes-mellitus-in-the-united-arab-emirates
#5
Agata Schubert, Anders T Buchholt, Antoine C El Khoury, Ahmed Kamal, Vanessa Taieb
OBJECTIVE: This study evaluates the cost of achieving glycemic control with 3 sodium glucose co-transporter 2 (SGLT2) inhibitors, canagliflozin, dapagliflozin, and empagliflozin, in patients with type 2 diabetes mellitus (T2DM) from the payer perspective in the United Arab Emirates (UAE). METHODS: A systematic literature review identified randomized controlled trials of antihyperglycemic agents as add-on to metformin in patients with T2DM of 26 ± 4 weeks in duration, published by 10 September 2014...
March 21, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28321056/sodium-glucose-co-transporter-2-inhibitors-reduce-the-abdominal-visceral-fat-area-and-may-influence-the-renal-function-in-patients-with-type-2-diabetes
#6
Takahiro Tosaki, Hideki Kamiya, Tatsuhito Himeno, Yoshiro Kato, Masaki Kondo, Kaori Toyota, Tomoyo Nishida, Megumi Shiroma, Kaori Tsubonaka, Hitomi Asai, Miho Moribe, Yuki Nakaya, Jiro Nakamura
Objective and Methods An SGLT2 inhibitor (ipragliflozin, dapagliflozin, luseogliflozin, tofogliflozin, or canagliflozin) was administered to 132 outpatients with type 2 diabetes mellitus with or without other antidiabetic drugs for 6 months to evaluate its efficacy, the incidence of adverse events, and its influence on the renal function. Results The patient's mean glycated hemoglobin level significantly improved from 7.52±1.16% to 6.95±0.98% (p<0.001). The body weight of the patients was significantly reduced from 78...
2017: Internal Medicine
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#7
Manisha Garg, Husam Ghanim, Nitesh D Kuhadiya, Kelly Green, Jeanne Hejna, Sanaa Abuaysheh, Barrett Torre, Manav Batra, Antoine Makdissi, Ajay Chaudhuri, Paresh Dandona
In view of the occurrence of diabetic ketoacidosis associated with the use of sodium-glucose transport protein-2 (SGLT2) inhibitors in patients with type 1 diabetes (T1DM) and the relative absence of this complication in patients treated with liraglutide in spite of reductions in insulin doses, we investigated the effect of liraglutide on ketogenesis. Twenty-six patients with inadequately controlled T1DM were randomly divided into two groups of 13 patients each. After an overnight fast, patients were injected, subcutaneously, with either liraglutide 1...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28304141/evidence-connecting-old-new-and-neglected-glucose-lowering-drugs-to-bile-acid-induced-glp-1-secretion-a-review
#8
REVIEW
Martin L Kårhus, Andreas Brønden, David P Sonne, Tina Vilsbøll, Fillip K Knop
Bile acids are amphipathic water-soluble steroid-based molecules best known for their important lipid-solubilizing role in the assimilation of fat. Recently, bile acids have emerged as metabolic integrators with glucose-lowering potential. Among a variety of gluco-metabolic effects, bile acids have been demonstrated to modulate the secretion of the gut-derived incretin hormone glucagon-like peptide-1 (GLP-1), possibly via the transmembrane receptor Takeda G protein-coupled receptor 5 (TGR5) and the nuclear farnesoid X receptor (FXR), in intestinal L cell...
March 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#9
REVIEW
Pieter Martens, Chantal Mathieu, Frederik H Verbrugge
This review provides mechanistic insight in the pleiotropic effects of sodium-glucose transporter-2 (SGLT-2) inhibitors with particular interest to the pathophysiology of heart failure. The SGLT-2 inhibitor empagliflozin has recently demonstrated an unprecedented 38% reduction in cardiovascular mortality in patients with diabetes. Despite modest effects on long-term glycemic control, highly significant reductions in heart failure admissions and end-stage kidney disease were observed. SGLT-2 inhibitors are the latest approved class of glucose-lowering agents...
March 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28295962/improving-glycemic-control-in-type-2-diabetes-stimulate-insulin-secretion-or-provide-beta-cell-rest
#10
REVIEW
Daniël H van Raalte, C Bruce Verchere
Type 2 diabetes (T2D) is characterized by a gradual decline of pancreatic beta cell function that determines the progressive course of the disease. While beta-cell failure is an important contributor to hyperglycemia, chronic hyperglycemia itself is also detrimental for beta-cell function, likely by inducing prolonged secretory stress on the beta cell as well as through direct glucotoxic mechanisms that have not been fully defined. For years, research has been carried out in search of therapies targeting hyperglycemia that preserve long-term beta-cell function in T2D, a quest that is still ongoing...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28295959/the-albuminuria-lowering-response-to-dapagliflozin-is-variable-and-reproducible-between-individual-patients
#11
Sergei I Petrykiv, Gozewijn D Laverman, Dick de Zeeuw, Hiddo J L Heerspink
AIMS: Albuminuria reduction is essential for renal and cardiovascular protection. We characterized the efficacy of dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, on albuminuria. Secondly, we assessed whether the albuminuria lowering effect varies between patients, and whether this variability in response is reproducible. MATERIAL AND METHODS: A double-blind, randomized, placebo controlled crossover trial was conducted. Patients with type 2 diabetes and albumin:creatinine ratio >100 mg/g on a stable dose of an Angiotensin Converting Enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) were enrolled...
March 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28279980/glucose-transporter-4-glut4-is-not-necessary-for-overload-induced-glucose-uptake-or-hypertrophic-growth-in-mouse-skeletal-muscle
#12
Shawna L McMillin, Denise L Schmidt, Barbara B Kahn, Carol A Witczak
Glucose transporter 4 (GLUT4) is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine if GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by unilateral synergist ablation. After 5 days, muscle weights and ex vivo [(3)H]-2-deoxy-D-glucose uptake were assessed. Overload-induced muscle glucose uptake and hypertrophic growth were not impaired in muscle-specific GLUT4 knockout mice, demonstrating that GLUT4 is not necessary for these processes...
March 9, 2017: Diabetes
https://www.readbyqxmd.com/read/28270893/association-of-whole-blood-viscosity-with-metabolic-syndrome-in-type-2-diabetic-patients-independent-association-with-post-breakfast-triglyceridemia
#13
Satomi Minato, Akiko Takenouchi, Junko Uchida, Ayaka Tsuboi, Miki Kurata, Keisuke Fukuo, Tsutomu Kazumi
BACKGROUND: Associations of whole blood viscosity (WBV) with metabolic syndrome (MS) have not been extensively studied in patients with type 2 diabetes. METHODS: Intrapersonal means of 12 measurements of waist circumference, blood pressure (BP) and high-density lipoprotein cholesterol and those of six measurements of fasting and post-breakfast triglycerides (TG) during 12 months were calculated in a cohort of 168 patients with type 2 diabetes. Based on these means, MS was diagnosed according to the modified National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of abdominal obesity...
April 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28255241/an-evidence-based-practice-oriented-review-focusing-on-canagliflozin-in-the-management-of-type-2-diabetes
#14
REVIEW
Joseph A Messana, Stanley S Schwartz, Raymond R Townsend
Caring for patients with type 2 diabetes mellitus (T2DM) has entered an era with many recent additions to the regimens used to clinically control their hyperglycemia. The most recent class of agents approved by the Food and Drug Administration (FDA) for T2DM is the sodium-glucose-linked transporter type 2 (SGLT2) inhibitors, which work principally in the proximal tubule of the kidney to block filtered glucose reabsorption. In the few years attending this new class arrival in the market, there has been a great deal of interest generated by the novel mechanism of action of SGLT2 inhibitors and by recent large outcome trials suggesting benefit on important clinical outcomes such as death, cardiovascular disease and kidney disease progression...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28254770/sglt2-inhibition-in-the-diabetic-kidney-from-mechanisms-to-clinical-outcome
#15
Erik J M van Bommel, Marcel H A Muskiet, Lennart Tonneijck, Mark H H Kramer, Max Nieuwdorp, Daniel H van Raalte
Diabetic kidney disease not only has become the leading cause for ESRD worldwide but also, highly contributes to increased cardiovascular morbidity and mortality in type 2 diabetes. Despite increased efforts to optimize renal and cardiovascular risk factors, like hyperglycemia, hypertension, obesity, and dyslipidemia, they are often insufficiently controlled in clinical practice. Although current drug interventions mostly target a single risk factor, more substantial improvements of renal and cardiovascular outcomes can be expected when multiple factors are improved simultaneously...
March 2, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28253918/luseogliflozin-reduces-epicardial-fat-accumulation-in-patients-with-type-2-diabetes-a-pilot-study
#16
Ryotaro Bouchi, Masahiro Terashima, Yuriko Sasahara, Masahiro Asakawa, Tatsuya Fukuda, Takato Takeuchi, Yujiro Nakano, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
BACKGROUND: Accumulation of epicardial fat (EF) is associated with increased cardio-metabolic risks and coronary events, independently of traditional cardiovascular risk factors. Therefore, the reduction of EF volume (EFV) may be associated with reduced cardio-metabolic risks and future cardiovascular events. Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce body fat including visceral fat and cardiovascular events in patients with type 2 diabetes. However, it has still been unknown whether SGLT2 inhibitors can reduce EFV...
March 3, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28251513/intensifying-treatment-beyond-monotherapy-in-type-2-diabetes-mellitus-where-do-newer-therapies-fit
#17
REVIEW
Alexander Kuhn, Jean Park, Adline Ghazi, Vanita R Aroda
PURPOSE OF REVIEW: Guidelines for a standard second diabetes medication for the treatment of type 2 diabetes (T2DM) have yet to be established. The rapid increase in the number of newer therapies available makes the choice more difficult. Thus, we reviewed clinical trial evidence evaluating newer therapies available for treatment intensification beyond monotherapy. RECENT FINDINGS: Head-to-head studies comparing newer therapies versus traditional (i.e., sulfonylurea) approaches consistently find lower incidence of hypoglycemia and weight gain with newer therapies...
March 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28249291/bile-acid-uptake-transporters-as-targets-for-therapy
#18
Davor Slijepcevic, Stan F J van de Graaf
Bile acids are potent signaling molecules that regulate glucose, lipid and energy homeostasis predominantly via the bile acid receptors farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor 5 (TGR5). The sodium taurocholate cotransporting polypeptide (NTCP) and the apical sodium dependent bile acid transporter (ASBT) ensure an effective circulation of (conjugated) bile acids. The modulation of these transport proteins affects bile acid localization, dynamics and signaling. The NTCP-specific pharmacological inhibitor myrcludex B inhibits hepatic uptake of conjugated bile acids...
2017: Digestive Diseases
https://www.readbyqxmd.com/read/28246292/correcting-postprandial-hyperglycemia-in-zucker-diabetic-fatty-rats-with-a-sglt2-inhibitor-restores-glucose-effectiveness-in-liver-and-reduces-insulin-resistance-in-skeletal-muscle
#19
Tracy P O'Brien, Erin C Jenkins, Shanea K Estes, Antonio V Castaneda, Kiichiro Ueta, Tiffany D Farmer, Allison E Puglisi, Larry L Swift, Richard L Printz, Masakazu Shiota
Ten-week-old ZDF rats at an early stage of diabetes embody metabolic characteristics of obese type 2 diabetic patients, severe insulin and glucose intolerance in muscle and liver, excessive postprandial excursion of plasma glucose and insulin, and a loss of metabolic flexibility with decreased lipid oxidation. Metabolic flexibility and glucose flux were examined in Zucker diabetic fatty (ZDF) rats during fasting and near normal postprandial insulinemia and glycemia after correcting excessive postprandial hyperglycemia by treatment with sodium-glucose co-transporter 2 inhibitor (SGLT2-I) for 7 days...
February 28, 2017: Diabetes
https://www.readbyqxmd.com/read/28244693/dapagliflozin-improves-insulin-resistance-and-glucose-intolerance-in-a-novel-transgenic-rat-with-chronic-glucose-overproduction-and-glucose-toxicity
#20
Christos N Joannides, Salvatore P Mangiafico, Matthew F Waters, Benjamin J Lamont, Sofianos Andrikopoulos
AIMS: Insulin resistance and impaired insulin secretion are cardinal defects that contribute to hyperglycemia in type 2 diabetes. Recently, a new class of drugs called sodium-glucose linked transporter 2 (SGLT2) inhibitors has been introduced that reduce blood glucose by inhibiting glucose reabsorption in the kidney and is not dependent on glucose metabolism or insulin action. The purpose of the present study was to determine whether the excretion of glucose would improve insulin resistance, impaired insulin secretion or both...
February 28, 2017: Diabetes, Obesity & Metabolism
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