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https://www.readbyqxmd.com/read/28332871/sodium-glucose-cotransporter-2-and-dipeptidyl-peptidase-4-inhibition-promise-of-a-dynamic-duo
#1
Ildiko Lingvay
OBJECTIVE: This article reviews evidence supporting sodium glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP-4) inhibitor combination therapy for management of type 2 diabetes mellitus (T2DM). METHODS: We conducted a non-systematic review of the literature focusing on single-pill or fixed-dose combinations of SGLT2 inhibitors and DPP-4 inhibitors available in the United States. RESULTS: SGLT2 inhibitors and DPP-4 inhibitors have complementary mechanisms of action that address several of the underlying pathophysiological abnormalities present in T2DM without overlapping toxicities...
March 23, 2017: Endocrine Practice
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
#2
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/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/28324025/clinical-and-genetic-features-of-patients-with-type-2-diabetes-and-renal-glycosuria
#4
Siqian Gong, Jiandong Guo, Xueyao Han, Meng Li, Lingli Zhou, Xiaoling Cai, Yu Zhu, Yingying Luo, Simin Zhang, Xianghai Zhou, Yumin Ma, Linong Ji
Context: A sodium glucose cotransporter 2 (SGLT2) inhibitor, which increases urinary glucose excretion, was recently reported to decrease blood glucose levels and deaths among patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. Mutations in SLC5A2 and HNF1A are associated with renal glycosuria, but their contributions to renal glycosuria in patients with T2DM are not well understood. Objective: To assess the clinical features of T2DM patients with renal glycosuria and those with low urinary glucose excretion (LUGE) and identify variants in the coding regions of SLC5A2 and HNF1A in patients with renal glycosuria and T2DM...
January 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-following-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#5
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
#6
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/28322073/sglt2-inhibitor-dpp-4-inhibitor-combination-therapy-complementary-mechanisms-of-action-for-management-of-type-2-diabetes-mellitus
#7
Jayant Dey
Type 2 diabetes mellitus is a progressive disease with multiple underlying pathophysiologic defects. Monotherapy alone cannot maintain glycemic control and leads to treatment failure. Ideally, a combination of glucose-lowering agents should have complementary mechanisms of action that address multiple pathophysiologic pathways, can be used at all stages of the disease, and be generally well tolerated with no increased risk of hypoglycemia, cardiovascular events, or weight gain. The combination should also provide conveniences for patients, such as oral dosing, single-pill formulations, and once-daily administration, potentially translating to improved adherence...
March 21, 2017: Postgraduate Medicine
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
#8
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/28319810/inhibitors-of-glut-slc2a-enhance-the-action-of-bcnu-and-temozolomide-against-high-grade-gliomas
#9
Alberto Azzalin, Giulia Nato, Elena Parmigiani, Francesca Garello, Annalisa Buffo, Lorenzo Magrassi
Glucose transport across glioblastoma membranes plays a crucial role in maintaining the enhanced glycolysis typical of high-grade gliomas and glioblastoma. We tested the ability of two inhibitors of the glucose transporters GLUT/SLC2A superfamily, indinavir (IDV) and ritonavir (RTV), and of one inhibitor of the Na/glucose antiporter type 2 (SGLT2/SLC5A2) superfamily, phlorizin (PHZ), in decreasing glucose consumption and cell proliferation of human and murine glioblastoma cells. We found in vitro that RTV, active on at least three different GLUT/SLC2A transporters, was more effective than IDV, a specific inhibitor of GLUT4/SLC2A4, both in decreasing glucose consumption and lactate production and in inhibiting growth of U87MG and Hu197 human glioblastoma cell lines and primary cultures of human glioblastoma...
March 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28304146/liraglutide-acutely-suppresses-glucagon-lipolysis-and-ketogenesis-in-type-1-diabetes
#10
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/28303514/euglycemic-ketosis-in-patients-with-type-2-diabetes-on-sglt2-inhibitor-therapy-an-emerging-problem-and-solutions-offered-by-diabetes-technology
#11
A Pfützner, D Klonoff, L Heinemann, N Ejskjaer, J Pickup
Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials...
March 17, 2017: Endocrine
https://www.readbyqxmd.com/read/28299616/promise-of-sglt2-inhibitors-in-heart-failure-diabetes-and-beyond
#12
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/28291655/the-cardiovascular-safety-trials-of-dpp-4-inhibitors-glp-1-agonists-and-sglt2-inhibitors
#13
REVIEW
Matthew H Secrest, Jacob A Udell, Kristian B Filion
In this paper, we review the results of large, double-blind, placebo-controlled randomized trials mandated by the US Food and Drug Administration to examine the cardiovascular safety of newly-approved antihyperglycemic agents in patients with type 2 diabetes. The cardiovascular effects of dipeptidyl peptidase-4 (DPP-4) inhibitors remain controversial: while these drugs did not reduce or increase the risk of primary, pre-specified composite cardiovascular outcomes, one DPP-4 inhibitor (saxagliptin) increased the risk of hospitalization for heart failure in the overall population; another (alogliptin) demonstrated inconsistent effects on heart failure hospitalization across subgroups of patients, and a third (sitagliptin) demonstrated no effect on heart failure...
January 28, 2017: Trends in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28277831/dapagliflozin-potential-beneficial-effects-in-the-prevention-and-treatment-of-renal-and-cardiovascular-complications-in-patients-with-type-2-diabetes
#14
Paola Fioretto, Angelo Avogaro
Diabetic kidney disease is the leading cause of end-stage renal disease, a significant contributor to cardiovascular (CV) disease, responsible for much of the morbidity and mortality in patients with type 2 diabetes (T2DM). Strategies to slow or prevent the onset and progression of diabetic kidney disease are critical for effectively managing T2DM and reducing CV risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective antidiabetic agents, which may provide nephroprotective and CV protective effects...
March 20, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276972/pharmacotherapy-of-treatment-resistant-type-2-diabetes
#15
André J Scheen
Despite type 2 diabetes (T2D) management offers a variety of pharmacological interventions targeting different defects, numerous patients remain with persistent hyperglycaemia responsible for severe complications. Unlike resistant hypertension, treatment resistant T2D is not a classical concept although it is a rather common observation in clinical practice. Areas covered: This article proposes a definition for 'treatment resistant diabetes', analyses the causes of poor glucose control despite standard therapy, briefly considers the alternative approaches to glucose-lowering pharmacotherapy and finally describes how to overcome poor glycaemic control, using innovative oral or injectable combination therapies...
March 1, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28276512/the-efficacy-and-safety-of-sglt2-inhibitors-for-adjunctive-treatment-of-type-1-diabetes-a-systematic-review-and-meta-analysis
#16
Jiao Chen, Fang Fan, J Y Wang, Yang Long, C L Gao, R C Stanton, Yong Xu
To assess the efficacy and safety of the SGLT-2 inhibitors as adjunct therapy to insulin in T1DM, clinical trials indexed in PubMed, Cochrane Library, EMbase from inception through April 5, 2016. A meta-analysis was conducted on trials of SGLT-2 inhibitors in patients with T1DM on insulin therapy using RevMan 5.3 software. Of the 371 articles identified, ten met eligibility criteria. Seven clinical trials including four randomized controlled trials and 581 patients were included. Compared with the control group, SGLT-2 inhibitors group had significantly reduced fasting plasma glucose by 0...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28262472/the-role-of-sodium-glucose-cotransporter-2-inhibitors-in-the-management-of-type-2-diabetes
#17
REVIEW
Oren Steen, Ronald M Goldenberg
Sodium-glucose cotransporter 2 (SGTL2) inhibitors are a novel class of antihyperglycemic agents that work in an insulin-independent manner by promoting urinary glucose excretion. In addition to efficacious glucose lowering, they exert beneficial effects on blood pressure and weight while avoiding hypoglycemia unless combined with insulin or insulin secretagogues. This review explores the mechanism of action of SGLT2 inhibitors, their effects on glycated hemoglobin, weight, blood pressure and hypoglycemia, potential adverse effects, renal considerations and cardiovascular outcomes...
March 3, 2017: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28255241/an-evidence-based-practice-oriented-review-focusing-on-canagliflozin-in-the-management-of-type-2-diabetes
#18
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
#19
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
#20
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
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