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https://www.readbyqxmd.com/read/28708480/optimizing-diabetes-treatment-in-the-presence-of-obesity
#1
REVIEW
Mary Angelynne Esquivel, M Cecilia Lansang
Evidence of a neurophysiologic mechanism that involves hormones from adipocytes, pancreatic islet cells, and the gastrointestinal tract implicated in both obesity and diabetes has led to a search for drugs that not only either target obesity and diabetes or reduce hemoglobin A1c, but also have weight loss as a potential side effect. The authors review medications approved for the treatment of type 2 diabetes mellitus (including pramlintide, also approved for type 1 diabetes) that also have weight loss as a side effect...
July 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/28699798/durability-of-response-to-dapagliflozin-a-review-of-long-term-efficacy-and-safety
#2
Serge Jabbour
BACKGROUND: Due to the chronic nature of type 2 diabetes (T2D), it is essential for an antidiabetic drug to have durable efficacy and a good long-term safety profile. Dapagliflozin is a member of a unique class of antidiabetic drugs that inhibit the sodium-glucose cotransporter 2 (SGLT-2) in the renal tubules and have an insulin-independent mechanism of action. In short-term studies (≤24 weeks), dapagliflozin reduced glycated hemoglobin (A1c), weight, and systolic blood pressure, and had a good safety profile...
July 12, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28686256/correction-synthesis-of-l-rhamnose-derived-chiral-bicyclic-triazoles-as-novel-sodium-glucose-transporter-sglt-inhibitors
#3
Siddamal Reddy Putapatri, Abhinav Kanwal, Balasubramanian Sridhar, Sanjay K Banerjee, Srinivas Kantevari
Correction for 'Synthesis of l-rhamnose derived chiral bicyclic triazoles as novel sodium-glucose transporter (SGLT) inhibitors' by Siddamal Reddy Putapatri et al., Org. Biomol. Chem., 2014, 12, 8415-8421.
July 19, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28677333/review-article-new-treatments-in-non-alcoholic-fatty-liver-disease
#4
REVIEW
S A Townsend, P N Newsome
BACKGROUND: Non-alcoholic fatty liver disease is the fastest growing cause of liver disease in the Western world, yet there is no approved pharmacotherapy. While lifestyle modifications remain the mainstay of treatment, only a proportion of individuals are able to make or sustain them, and so more treatment options are required. AIM: To review the potential benefit of drugs used in clinical practice, those entering phase II trials, and compounds being investigated in pre-clinical studies...
July 4, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28667491/sglt-2-inhibitors-in-heart-failure-implications-for-the-kidneys
#5
REVIEW
Frederik H Verbrugge, Pieter Martens, Wilfried Mullens
PURPOSE OF REVIEW: This review aims to summarize the renal effects of sodium-glucose transporter-2 (SGLT-2) inhibitors and their potential implications in heart failure pathophysiology. RECENT FINDINGS: In patients with diabetes and established atherosclerosis, the SGLT-2 inhibitor empagliflozin versus placebo significantly reduced the rate of heart failure admissions with 35%. Moreover, empagliflozin slowed kidney disease progression and reduced the need for renal replacement therapy...
June 30, 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28665967/effects-of-canagliflozin-on-weight-loss-in-high-fat-diet-induced-obese-mice
#6
Wenjun Ji, Mei Zhao, Meng Wang, Wenhui Yan, Yuan Liu, Shuting Ren, Jun Lu, Bing Wang, Lina Chen
Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been shown to reduce body weight during the treatment of type 2 diabetes mellitus (T2DM). In this study, we sought to determine the role of canagliflozin in body weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive control. The body weight, liver weight, liver morphology, total cholesterol (TC) and triglyceride (TG) levels were examined...
2017: PloS One
https://www.readbyqxmd.com/read/28656707/efficacy-and-safety-of-sodium-glucose-cotransporter-2-inhibitors-versus-dipeptidyl-peptidase-4-inhibitors-as-monotherapy-or-add-on-to-metformin-in-patients-with-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis
#7
Zhiying Wang, Jiahui Sun, Ruobing Han, Dongzhu Fan, Xinyi Dong, Zenghui Luan, Rongwu Xiang, Mingyi Zhao, Jingyu Yang
AIMS: To compare the efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) as monotherapy or add-on to metformin (Met) in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: PubMed, Embase, and ClinicalTrials.gov were systematically searched for randomized controlled trials to assess the efficacy and safety of DPP-4is and SGLT-2is in patients with T2DM. Risk ratio (RR) and weighted mean difference (WMD) were used to evaluate the outcomes...
June 28, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28647919/role-of-sglt2-inhibitors-in-patients-with-diabetes-mellitus-and-heart-failure
#8
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/28625822/comparison-of-the-expression-and-spatial-localization-of-glucose-transporters-in-the-rat-bovine-and-human-lens
#9
Julie C Lim, Rebecca D Perwick, Bo Li, Paul J Donaldson
The energy required to drive lens transparency is derived from the metabolism of glucose. In the lens, the uptake of glucose is likely to involve either facilitative glucose uptake mediated by members of the GLUT family or Na(+) dependent glucose uptake via members of the SGLT family, or both. While GLUT1 and GLUT3 have previously been identified in the rat lens, the expression of SGLTs is unknown. Since antibodies directed against the N and C-terminal epitopes of the GLUT and SGLT family are now commercially available, the purpose of this study is to extend our screening of glucose transporters in the rat lens to include the SGLTs and compare the expression profiles of GLUTs and SGLTs in the different regions of the rat, bovine and human lens...
June 15, 2017: Experimental Eye Research
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
#10
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
#11
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
#12
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...
June 2017: EBioMedicine
https://www.readbyqxmd.com/read/28570924/effects-of-sglt-2-inhibitors-on-diabetic-ketoacidosis-a-meta-analysis-of-randomised-controlled-trials
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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 14, 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
#19
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
#20
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
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