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SGLT-2 Inhibitors

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https://www.readbyqxmd.com/read/28647919/role-of-sglt2-inhibitors-in-patients-with-diabetes-mellitus-and-heart-failure
#1
REVIEW
Frederik H Verbrugge
PURPOSE OF REVIEW: This review aims to summarize the evidence on cardiovascular risks and benefits of glucose-lowering drugs in diabetic patients, with a particular focus on the role of sodium-glucose transporter-2 (SGLT-2) inhibitors and their promising potential as a heart failure treatment. RECENT FINDINGS: The SGLT-2 inhibitor empagliflozin has emerged as the first glucose-lowering drug to lower cardiovascular mortality in diabetes with an unprecedented 38% relative risk reduction...
June 24, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28593615/a-single-dose-of-dapagliflozin-an-sglt-2-inhibitor-induces-higher-glycosuria-in-gck-and-hnf1a-mody-than-in-type-2-diabetes-mellitus
#2
J Hohendorff, M Szopa, J Skupien, M Kapusta, B Zapala, T Platek, S Mrozinska, T Parpan, W Glodzik, A Ludwig-Galezowska, B Kiec-Wilk, T Klupa, M T Malecki
AIMS: SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. METHODS: We examined 14 HNF1A-MODY, 19 GCK-MODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes...
June 7, 2017: Endocrine
https://www.readbyqxmd.com/read/28582367/do-effects-of-sodium-glucose-cotransporter-2-inhibitors-in-patients-with-diabetes-give-insight-into-potential-use-in-non-diabetic-kidney-disease
#3
Harindra Rajasekeran, David Z Cherney, Julie A Lovshin
PURPOSE OF REVIEW: Our aim was to review the rationale for the role of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) as renoprotective therapy in patients with and without diabetes. RECENT FINDINGS: SGLT-2i are antihyperglycemic agents, approved for treating type 2 diabetes to reduce glycosylated hemoglobin, type A1c. Primary glucoregulatory effects occur through selective inhibition of SGLT-2 at the renal proximal tubule promoting glucosuria leading to blood glucose lowering...
June 2, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28579299/sglt2-inhibition-by-empagliflozin-promotes-fat-utilization-and-browning-and-attenuates-inflammation-and-insulin-resistance-by-polarizing-m2-macrophages-in-diet-induced-obese-mice
#4
Liang Xu, Naoto Nagata, Mayumi Nagashimada, Fen Zhuge, Yinhua Ni, Guanliang Chen, Eric Mayoux, Shuichi Kaneko, Tsuguhito Ota
Sodium-glucose cotransporter (SGLT) 2 inhibitors increase urinary glucose excretion (UGE), leading to blood glucose reductions and weight loss. However, the impacts of SGLT2 inhibition on energy homeostasis and obesity-induced insulin resistance are less well known. Here, we show that empagliflozin, a SGLT2 inhibitor, enhanced energy expenditure and attenuated inflammation and insulin resistance in high-fat-diet-induced obese (DIO) mice. C57BL/6J mice were pair-fed a high-fat diet (HFD) or a HFD with empagliflozin for 16weeks...
May 26, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28570924/effects-of-sglt-2-inhibitors-on-diabetic-ketoacidosis-a-meta-analysis-of-randomised-controlled-trials
#5
Matteo Monami, Besmir Nreu, Stefania Zannoni, Carlotta Lualdi, Edoardo Mannucci
AIMS: Diabetic ketoacidosis (DKA) associated with SGLT-2 inhibitors (SGLT-2i) is a possible adverse event. In fact, SGLT-2i are capable of stimulating the release of glucagon and ketone re-absorption in the renal tubuli, thus increasing the concentration of ketone bodies. METHODS: A Medline search for SGLT2i (dapagliflozin, empagliflozin, canagliflozin, ipragliflozin, ertugliflozin, luseogliflozin) was performed, collecting all randomized trials with a duration of treatment≥12weeks, enrolling patients with type 2 diabetes, and comparing a SGLT2i with placebo or other comparators...
May 18, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28550195/dipeptidyl-peptidase-4-inhibition-stimulates-distal-tubular-natriuresis-and-increases-in-circulating-sdf-1%C3%AE-1-67-in-patients-with-type-2-diabetes
#6
Julie A Lovshin, Harindra Rajasekeran, Yulyia Lytvyn, Leif E Lovblom, Shajiha Khan, Robel Alemu, Amy Locke, Vesta Lai, Huaibing He, Lucinda Hittle, Weixun Wang, Daniel J Drucker, David Z I Cherney
OBJECTIVE: Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium-glucose cotransporter 2 (SGLT-2) inhibitors, we examined whether and how sitagliptin modulates fractional sodium excretion and renal and systemic hemodynamic function. RESEARCH DESIGN AND METHODS: We studied 32 patients with type 2 diabetes in a prospective, double-blind, randomized, placebo-controlled trial...
May 26, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28544369/american-association-of-clinical-endocrinologists-2017
#7
EDITORIAL
Abigail E Dove, Payal H Marathe, Helen X Gao, Kelly L Close
The 26th annual scientific and clinical sessions of the American Association of Clinical Endocrinologists (AACE) gathered in Austin, TX, USA from May 3-7, 2017. The meeting included little in the way of new data, but was rich in commentary from leaders in the diabetes field, particularly with regard to sodium/glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists. In a deep-dive session on the renal effects of SGLT-2 inhibitors, both Dr Ralph DeFronzo and DrMatthew Weir were extremely positive about the renal benefit of these agents and expressed strong confidence that the benefits extend to all members of the class...
May 23, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28536852/the-role-of-sglt-2-inhibitors-as-part-of-optimal-medical-therapy-in-improving-cardiovascular-outcomes-in-patients-with-diabetes-and-coronary-artery-disease
#8
Wassim Mosleh, Abhinav Sharma, Mandeep S Sidhu, Brian Page, Umesh C Sharma, Michael E Farkouh
The optimal treatment approach to patients with coronary artery disease (CAD), including those with type 2 diabetes mellitus (T2DM), has been extensively evaluated. Several trials of stable ischemic heart disease including patients with T2DM have demonstrated that medical management is comparable to revascularization in terms of mortality and rates of major adverse cardiovascular events (MACE). There has been a growing appreciation for optimal medical therapy's (OMT) role in improving clinical outcomes. It is vital to target T2DM patients to prevent or delay MACE events through advanced OMT, ultimately delaying if not avoiding the need for revascularization...
May 24, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28535688/sglt-2-inhibitors-is-there-a-role-in-type-1-diabetes-mellitus-management
#9
Nabila Ahmed-Sarwar, Angela K Nagel, Samantha Leistman, Kevin Heacock
OBJECTIVE: The purpose of this review is to identify and evaluate disease management of patients with type 1 diabetes mellitus (T1DM) who were treated with a sodium-glucose cotransporter 2 (SGLT-2) inhibitor as an adjunct to insulin therapy. DATA SOURCES: A PubMed (1969 to March 2017) and Ovid (1946 to March 2017) search was performed for articles published utilizing the following MESH terms: canagliflozin, empagliflozin, dapagliflozin, type 1 diabetes mellitus, insulin dependent diabetes, insulin, sodium-glucose transporter 2...
May 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28535336/transport-of-the-glucosamine-derived-browning-product-fructosazine-polyhydroxyalkylpyrazine-across-the-human-intestinal-caco-2-cell-monolayer-role-of-the-hexose-transporters
#10
Abhishek Bhattacherjee, Yuliya Hrynets, Mirko Betti
The transport mechanism of fructosazine, a glucosamine self-condensation product, was investigated using a Caco-2 cell model. Fructosazine transport was assessed by measuring the bidirectional permeability coefficient across Caco-2 cells. The mechanism of transport was evaluated using phlorizin, an inhibitor of sodium-dependent glucose cotransporters (SGLT) 1 and 2, phloretin and quercetin, inhibitors of glucose transporters (GLUT) 1 and 2, transcytosis inhibitor wortmannin, and gap junction disruptor cytochalasin D...
June 1, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28535208/sodium-glucose-cotransporter-2-in-mesangial-cells-and-retinal-pericytes-and-its-implications-for-diabetic-nephropathy-and-retinopathy
#11
Masarori Wakisaka, Tetsuhiko Nagao
Retinopathy and nephropathy are life-threatening diabetic complications that decrease patient quality of life. Although the mechanisms underlying these conditions have been extensively studied, they remain unknown. Recent reports have demonstrated the presence of SGLT2 in retinal pericytes and mesangial cells. Hyperglycemia results in functional and morphological changes in these cells, but these effects are attenuated by phlorizin, a non-selective SGLT inhibitor. Based on these findings, we hypothesized that SGLT2 plays a pivotal role in the development of diabetic nephropathy and retinopathy and that SGLT2 inhibitors may directly protect against these complications...
May 23, 2017: Glycobiology
https://www.readbyqxmd.com/read/28526540/sodium-dependent-glucose-transporters-sglt-in-human-ischemic-heart-a-new-potential-pharmacological-target
#12
Alessandra Di Franco, Giulia Cantini, Alessia Tani, Raffaele Coppini, Sandra Zecchi-Orlandini, Laura Raimondi, Michaela Luconi, Edoardo Mannucci
BACKGROUND: Empagliflozin is reported to reduce cardiovascular mortality and the rate of hospitalization for heart failure in type 2 diabetic patients with prior cardiovascular events. The mechanisms underlying the cardiac effects of this sodium/glucose transporter 2 (SGT2) inhibitor have not yet been clarified, though a direct action of the drug on the cardiomyocytes could be hypothesized. The aim of the present study is to assess the relative expression of SGLT2 and SGLT1, the two most relevant members of the SGLT family being potentially responsive to empagliflozin, in normal, ischemic and hypertrophic human hearts...
May 9, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28524098/sglt2-inhibitors-as-a-therapeutic-option-for-diabetic-nephropathy
#13
REVIEW
Daiji Kawanami, Keiichiro Matoba, Yusuke Takeda, Yosuke Nagai, Tomoyo Akamine, Tamotsu Yokota, Kazunori Sango, Kazunori Utsunomiya
Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium-glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28522450/lower-risk-of-heart-failure-and-death-in-patients-initiated-on-sglt-2-inhibitors-versus-other-glucose-lowering-drugs-the-cvd-real-study
#14
Mikhail Kosiborod, Matthew A Cavender, Alex Z Fu, John P Wilding, Kamlesh Khunti, Reinhard W Holl, Anna Norhammar, Kåre I Birkeland, Marit Jørgensen, Marcus Thuresson, Niki Arya, Johan Bodegård, Niklas Hammar, Peter Fenici
Background -Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose co-transporter-2 inhibitor (SGLT-2i) empagliflozin in type 2 diabetes patients with atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose lowering drugs (oGLDs) in six countries to determine if these benefits are seen in real-world practice, and across SGLT-2i class. Methods -Data were collected via medical claims, primary care/hospital records and national registries from the US, Norway, Denmark, Sweden, Germany and the UK...
May 18, 2017: Circulation
https://www.readbyqxmd.com/read/28511711/sglt2-inhibitors-a-novel-choice-for-the-combination-therapy-in-diabetic-kidney-disease
#15
REVIEW
Honghong Zou, Baoqin Zhou, Gaosi Xu
Diabetic kidney disease (DKD) is the most common cause of end stage renal disease. The comprehensive management of DKD depends on combined target-therapies for hyperglycemia, hypertension, albuminuria, and hyperlipaemia, etc. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, the most recently developed oral hypoglycemic agents acted on renal proximal tubules, suppress glucose reabsorption and increase urinary glucose excretion. Besides improvements in glycemic control, they presented excellent performances in direct renoprotective effects and the cardiovascular (CV) safety by decreasing albuminuria and the independent CV risk factors such as body weight and blood pressure, etc...
May 16, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28506962/pair-feeding-but-not-insulin-phloridzin-or-rosiglitazone-treatment-curtails-markers-of-beta-cell-dedifferentiation-in-db-db-mice
#16
Emi Ishida, Ja Young Kim-Muller, Domenico Accili
Beta cell failure is a hallmark of type 2 diabetes. Among several cellular biological mechanisms of cellular dysfunction, we and others have recently proposed that dedifferentiation of beta cells can explain the slowly progressive onset and partial reversibility of beta-cell failure. Accordingly, we provided evidence of such processes in humans and experimental animal models of insulin-resistant diabetes. In this study, we asked whether beta cell dedifferentiation can be prevented with diet or pharmacological treatment of diabetes...
May 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28506912/characterization-and-comparison-of-sglt2-inhibitors-part-3-effects-on-diabetic-complications-in-type-2-diabetic-mice
#17
Atsuo Tahara, Toshiyuki Takasu, Masanori Yokono, Masakazu Imamura, Eiji Kurosaki
In this study, we investigated and compared the effects of all six sodium-glucose cotransporter (SGLT) 2 inhibitors commercially available in Japan on diabetes-related diseases and complications in type 2 diabetic mice. Following 4-week repeated administration to diabetic mice, all SGLT2 inhibitors showed significant improvement in diabetes-related diseases and complications, including obesity; abnormal lipid metabolism; steatohepatitis; inflammation; endothelial dysfunction; and nephropathy. While all SGLT2 inhibitors exerted comparable effects in reducing hyperglycemia, improvement of these diabetes-related diseases and complications was more potent with the two long-acting drugs (ipragliflozin and dapagliflozin) than with the four intermediate-acting four drugs (tofogliflozin, canagliflozin, empagliflozin, and luseogliflozin), albeit without statistical significance...
May 12, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28490565/efficacy-and-safety-of-ipragliflozin-and-metformin-for-visceral-fat-reduction-in-patients-with-type-2-diabetes-receiving-treatment-with-dipeptidyl-peptidase-4-inhibitors-in-japan-a-study-protocol-for-a-prospective-multicentre-blinded-endpoint-phase-iv-randomised
#18
Masaya Koshizaka, Ko Ishikawa, Takahiro Ishikawa, Kazuki Kobayashi, Minoru Takemoto, Takuro Horikoshi, Ryota Shimofusa, Sho Takahashi, Kengo Nagashima, Yasunori Sato, Ichiro Tatsuno, Takashi Terano, Naotake Hashimoto, Nobuichi Kuribayashi, Daigaku Uchida, Koutaro Yokote
INTRODUCTION: In Japan, dipeptidyl peptidase-4 (DPP-4) inhibitors are frequently used as the treatment of choice for patients with type 2 diabetes. In some cases, however, poor glycaemic and body weight control issues persist despite treatment with DPP-4 inhibitors. Previous researchers have revealed that sodium-dependent glucose transporter-2 (SGLT-2) inhibitors reduce both plasma glucose levels and body weight in patients with type 2 diabetes. However, further investigation regarding the effects of SGLT-2 inhibitors on body composition, especially in the Asian population who tends to have relatively low-to-moderate body mass indices, is required...
May 9, 2017: BMJ Open
https://www.readbyqxmd.com/read/28490557/the-effect-of-empagliflozin-on-oxidative-nucleic-acid-modifications-in-patients-with-type-2-diabetes-protocol-for-a-randomised-double-blinded-placebo-controlled-trial
#19
Emil List Larsen, Vanja Cejvanovic, Laura Kofoed Kjær, Tina Vilsbøll, Filip Krag Knop, Jørgen Rungby, Henrik Enghusen Poulsen
INTRODUCTION: Cardiovascular disease is the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D). Although glycaemic control reduces microvascular complications, the effect of intensive treatment strategies or individual drugs on macrovascular diseases is still debated. RNA oxidation is associated with increased mortality in patients with T2D. Inspired by animal studies showing effect of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor (empagliflozin) on oxidative stress and a recent trial evaluating empagliflozin that demonstrated improved cardiovascular outcomes in patients with T2D at high risk of cardiovascular events, we hypothesise that empagliflozin lowers oxidative stress...
May 9, 2017: BMJ Open
https://www.readbyqxmd.com/read/28480956/the-renal-effects-of-sglt-2-inhibitors-and-other-anti-diabetic-drugs-clinical-relevance-and-potential-risks
#20
REVIEW
Eirini Lioudaki, Martin Whyte, Emmanouil S Androulakis, Konstantinos G Stylianou, Eugene K Dafnis, Emmanouil S Ganotakis
No abstract text is available yet for this article.
May 8, 2017: Clinical Pharmacology and Therapeutics
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