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https://www.readbyqxmd.com/read/27865185/a-new-era-in-the-management-of-type-2-diabetes-is-cardioprotection-at-long-last-a-reality
#1
EDITORIAL
Xavier Rossello, Derek M Yellon
The EMPA-REG OUTCOME and the LEADER trials have revealed a new era in the management of type 2 diabetes. The SGLT2 inhibitor empagliflozin demonstrated a lower rate of the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke compared to placebo. Liraglutide, a GLP-1 analogue, succeeded to demonstrate reduction on a composite outcome including first occurrence of cardiovascular death, nonfatal myocardial infarction or non-fatal stroke. These two medications act through different mechanisms and has consequently shown different patterns of cardiovascular benefit...
November 12, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27863704/cardiovascular-effects-of-glucose-lowering-therapies-for-type-2-diabetes-new-drugs-in-perspective
#2
REVIEW
Peter L Thompson, Timothy M E Davis
PURPOSE: The purpose of this study was to review the results of clinical trials assessing the cardiovascular effects of drugs for type 2 diabetes and the cardiovascular effects of newer available drugs. METHODS: We performed a detailed search of PubMed-listed publications, reports from international meetings, and ongoing studies from clinical trials.gov. FINDINGS: Currently available drugs have neutral or, in some cases, negative effects on cardiovascular outcomes...
November 15, 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27862902/cardiovascular-events-and-all-cause-mortality-associated-with-sulfonylureas-compared-to-other-antihyperglycaemic-drugs-a-bayesian-meta-analysis-of-survival-data
#3
Steve Bain, Eric Druyts, Chakrapani Balijepalli, Carl A Baxter, Craig Currie, Romita Das, Richard Donnelly, Kamlesh Khunti, Haya Langerman, Paul Leigh, Gaye Siliman, Kristian Thorlund, Kabirraaj Toor, Jiten Vora, Edward J Mills
AIM: Our aim was to conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulfonylureas versus other antihyperglycaemic drugs in patients with type 2 diabetes. MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane, and clinicaltrials.gov was conducted comparing sulfonylurea to placebo or other antihyperglycaemic drugs in patients with type 2 diabetes. A cloglog model was employed in the Bayesian framework to obtain comparative hazard ratios between interventions...
November 14, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27856285/neurotrophic-and-neuroprotective-effects-of-oxyntomodulin-in-neuronal-cells-and-a-rat-model-of-stroke
#4
Yazhou Li, Kou-Jen Wu, Seong-Jin Yu, Ian A Tamargo, Yun Wang, Nigel H Greig
Proglucagon-derived peptides, especially glucagon-like peptide-1 (GLP-1) and its long-acting mimetics, have exhibited neuroprotective effects in animal models of stroke. Several of these peptides are in clinical trials for stroke. Oxyntomodulin (OXM) is a proglucagon-derived peptide that co-activates the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR). The neuroprotective action of OXM, however, has not been thoroughly investigated. In this study, the neuroprotective effect of OXM was first examined in human neuroblastoma (SH-SY5Y) cells and rat primary cortical neurons...
November 14, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/27835045/cardiovascular-outcomes-of-new-medications-for-type-2-diabetes
#5
Jennifer M Trujillo, Sara A Wettergreen, Wesley A Nuffer, Samuel L Ellis, Michael T McDermott
Cardiovascular (CV) disease remains the leading cause of death in people with diabetes, highlighting the importance of using treatment options that do not increase CV risk or possibly decrease CV outcomes. Since 2008, the Food and Drug Administration has required demonstration of CV safety for all new medications developed for the glycemic management of diabetes. Seven trials have been published that have established CV safety for three DPP-4 inhibitors (alogliptin, saxagliptin, and sitagliptin), three GLP-1 receptor agonists (liraglutide, lixisenatide, and semaglutide), and one sodium-glucose cotransporter-2 inhibitor (empagliflozin)...
November 11, 2016: Diabetes Technology & Therapeutics
https://www.readbyqxmd.com/read/27777261/heart-rate-acceleration-with-glp-1-receptor-agonists-in-type-2-diabetes-patients-an-acute-and-12-week-randomised-double-blind-placebo-controlled-trial
#6
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Trynke Hoekstra, Mhh Kramer, Michaela Diamant, Daniël H van Raalte
OBJECTIVE: To examine mechanisms underlying resting heart rate (RHR) increments of GLP-1 receptor agonists in type 2 diabetes patients. DESIGN: Acute and 12-week randomised placebo-controlled, double-blind, single-centre parallel-group trial. METHODS: 57 type 2 diabetes patients (mean±SD age 62.8±6.9 years; BMI 31.8±4.1 kg/m2; HbA1c 7.3±0.6%), treated with metformin and/or sulfonylureas, were included between July 2013 and August 2015...
October 24, 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27698937/activation-of-glp-1-receptor-enhances-neuronal-base-excision-repair-via-pi3k-akt-induced-expression-of-apurinic-apyrimidinic-endonuclease-1
#7
Jenq-Lin Yang, Wei-Yu Chen, Yin-Ping Chen, Chao-Ying Kuo, Shang-Der Chen
Glucagon-like peptide-1 (GLP-1) is an intestinal-secreted incretin that increases cellular glucose up-take to decrease blood sugar. Recent studies, however, suggest that the function of GLP-1 is not only to decrease blood sugar, but also acts as a neurotrophic factor that plays a role in neuronal survival, neurite outgrowth, and protects synaptic plasticity and memory formation from effects of β-amyloid. Oxidative DNA damage occurs during normal neuron-activity and in many neurological diseases. Our study describes how GLP-1 affected the ability of neurons to ameliorate oxidative DNA damage...
2016: Theranostics
https://www.readbyqxmd.com/read/27566245/the-glucagon-like-peptide-1-receptor-agonist-exendin-4-ameliorates-warfarin-associated-hemorrhagic-transformation-after-cerebral-ischemia
#8
Fangzhe Chen, Weifeng Wang, Hongyan Ding, Qi Yang, Qiang Dong, Mei Cui
BACKGROUND: As the number of patients with cardioembolic ischemic stroke is predicted to be double by 2030, increased burden of warfarin-associated hemorrhagic transformation (HT) after cerebral ischemia is an expected consequence. However, thus far, no effective treatment strategy is available for HT prevention in routine clinical practice. While the glucagon-like peptide-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) is known to protect against oxidative stress and neuronal cell death caused by ischemic brain damage, its effect on preventing warfarin-associated HT after cerebral ischemia is yet unknown...
2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27514514/continued-efforts-to-translate-diabetes-cardiovascular-outcome-trials-into-clinical-practice
#9
REVIEW
Angelo Avogaro, Gian Paolo Fadini, Giorgio Sesti, Enzo Bonora, Stefano Del Prato
Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed...
2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27434443/comparison-of-clinical-outcomes-and-adverse-events-associated-with-glucose-lowering-drugs-in-patients-with-type-2-diabetes-a-meta-analysis
#10
Suetonia C Palmer, Dimitris Mavridis, Antonio Nicolucci, David W Johnson, Marcello Tonelli, Jonathan C Craig, Jasjot Maggo, Vanessa Gray, Giorgia De Berardis, Marinella Ruospo, Patrizia Natale, Valeria Saglimbene, Sunil V Badve, Yeoungjee Cho, Annie-Claire Nadeau-Fredette, Michael Burke, Labib Faruque, Anita Lloyd, Nasreen Ahmad, Yuanchen Liu, Sophanny Tiv, Natasha Wiebe, Giovanni F M Strippoli
IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis...
July 19, 2016: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/27373139/novel-antidiabetic-drugs-and-cardiovascular-risk-primum-non-nocere
#11
R C Bonadonna, C Borghi, A Consoli, M Volpe
AIMS: Diabetes treatments aim at preventing undesirable metabolic effects of hyperglycemia and at preventing/reducing tissue damage, including cardiovascular (CV) events. For approval, novel diabetes drugs undergo early systematic investigation to assess CV safety. This review provides an updated analysis of the results of recent studies examining novel diabetes medications and CV outcomes. DATA SYNTHESIS: The new regulatory guidelines enforce adjudication of all CV events when testing novel diabetes drugs...
September 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
https://www.readbyqxmd.com/read/27282621/cardiovascular-safety-of-glucose-lowering-agents-as-add-on-medication-to-metformin-treatment-in-type-2-diabetes-report-from-the-swedish-national-diabetes-register
#12
Nils Ekström, Ann-Marie Svensson, Mervete Miftaraj, Stefan Franzén, Björn Zethelius, Björn Eliasson, Soffia Gudbjörnsdottir
AIM: To investigate the relative safety of various glucose-lowering agents as add-on medication to metformin in type 2 diabetes in an observational study linking five national health registers. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes who had been on metformin monotherapy and started another agent in addition to metformin were eligible for inclusion. The study period was 2005-2012. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of mortality, cardiovascular disease (CVD), coronary heart disease (CHD), stroke and congestive heart failure (CHF) were estimated using Cox proportional hazards models, weighted for a propensity score...
October 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27240461/the-neuroprotection-of-liraglutide-against-ischaemia-induced-apoptosis-through-the-activation-of-the-pi3k-akt-and-mapk-pathways
#13
Huili Zhu, Yusheng Zhang, Zhongshan Shi, Dan Lu, Tingting Li, Yan Ding, Yiwen Ruan, Anding Xu
Glucagon-like peptide-1 (GLP-1) is an incretin hormone that increases glucose-dependent insulin secretion to reduce the glucose level. Liraglutide, a long-acting GLP-1 analogue, has been found to have neuroprotective action in various experimental models. However, the protective mechanisms of liraglutide in ischaemic stroke remain unclear. Here, we demonstrated that liraglutide significantly decreased the infarct volume, improved neurologic deficits, and lowered stress-related hyperglycaemia without causing hypoglycaemia in a rat model of middle cerebral artery occlusion (MCAO)...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27234258/obesity-alters-molecular-and-functional-cardiac-responses-to-ischemia-reperfusion-and-glucagon-like-peptide-1-receptor-agonism
#14
Daniel J Sassoon, Adam G Goodwill, Jillian N Noblet, Abass M Conteh, B Paul Herring, Jeanette N McClintick, Johnathan D Tune, Kieren J Mather
This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours...
July 2016: Basic Research in Cardiology
https://www.readbyqxmd.com/read/27217068/cardiovascular-events-and-all-cause-mortality-with-insulin-versus-glucagon-like-peptide-1-analogue-in-type-2-diabetes
#15
Uchenna Anyanwagu, Jil Mamza, Rajnikant Mehta, Richard Donnelly, Iskandar Idris
OBJECTIVES: To analyse time to cardiovascular events and mortality in patients with type 2 diabetes (T2D) who received treatment intensification with insulin or a glucagon-like peptide-1 (GLP-1ar) analogue following dual therapy failure with metformin (MET) and sulphonylurea (SU). METHODS: A retrospective cohort study was conducted in 2003 patients who were newly treated with a GLP-1ar or insulin following dual therapy (MET+SU) failure between 2006 and 2014. Data were sourced from The Health Improvement Network database...
October 1, 2016: Heart: Official Journal of the British Cardiac Society
https://www.readbyqxmd.com/read/27210264/empa-reg-and-other-cardiovascular-outcome-trials-of-glucose-lowering-agents-implications-for-future-treatment-strategies-in-type-2-diabetes-mellitus
#16
Guntram Schernthaner, Marie Helene Schernthaner-Reiter, Gerit-Holger Schernthaner
During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease...
June 2016: Clinical Therapeutics
https://www.readbyqxmd.com/read/27129676/low-calorie-sweetener-use-and-energy-balance-results-from-experimental-studies-in-animals-and-large-scale-prospective-studies-in-humans
#17
REVIEW
Sharon P G Fowler
For more than a decade, pioneering animal studies conducted by investigators at Purdue University have provided evidence to support a central thesis: that the uncoupling of sweet taste and caloric intake by low-calorie sweeteners (LCS) can disrupt an animal's ability to predict the metabolic consequences of sweet taste, and thereby impair the animal's ability to respond appropriately to sweet-tasting foods. These investigators' work has been replicated and extended internationally. There now exists a body of evidence, from a number of investigators, that animals chronically exposed to any of a range of LCSs - including saccharin, sucralose, acesulfame potassium, aspartame, or the combination of erythritol+aspartame - have exhibited one or more of the following conditions: increased food consumption, lower post-prandial thermogenesis, increased weight gain, greater percent body fat, decreased GLP-1 release during glucose tolerance testing, and significantly greater fasting glucose, glucose area under the curve during glucose tolerance testing, and hyperinsulinemia, compared with animals exposed to plain water or - in many cases - even to calorically-sweetened foods or liquids...
October 1, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/27010644/cardiovascular-outcome-studies-in-diabetes-how-do-we-make-sense-of-these-new-data
#18
REVIEW
W David Strain, Christine Smith
Poorly controlled diabetes is characterized by premature cardiovascular mortality and morbidity. The mechanisms linking hyperglycemia with accelerated atherosclerotic disease have not been fully elucidated; however, are thought to be mediated through vascular inflammation, oxidative stress and endothelial dysfunction. The advent of incretin-based therapy, whether by increasing endogenous glucagon-like peptide (GLP)-1 and glucose-dependent inhibitory polypeptide by inhibition of their breakdown using di-peptidyl peptidase 4 inhibitors, or augmenting GLP-1 activity using either exendin-4-based drugs or synthetic GLP-1 analogs promised not just improvements in glycemic control, but improvements in endothelial function, lipid profiles and markers of vascular inflammation...
June 2016: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/27003762/comparative-cardiovascular-safety-of-glucagon-like-peptide-1-receptor-agonists-versus-other-antidiabetic-drugs-in-routine-care-a-cohort-study
#19
E Patorno, B M Everett, A B Goldfine, R J Glynn, J Liu, C Gopalakrishnan, S C Kim
AIMS: To evaluate the comparative cardiovascular disease (CVD) safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in head-to-head comparisons with dipeptidyl peptidase-4 (DPP-4) inhibitors, sulphonylureas or insulin, when added to metformin, as used in 'real-world' patients with type 2 diabetes mellitus (T2DM). METHODS: Within a large US commercial health plan database linked to laboratory test results, we identified three pairwise 1 : 1 propensity-score-matched cohorts of patients with T2DM aged ≥18 years treated with metformin who initiated a GLP-1 RA or a comparator, i...
August 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/26911582/rationale-and-design-of-short-term-exenatide-therapy-in-acute-ischaemic-stroke-stexas-a-randomised-open-label-parallel-group-study
#20
Rachel T McGrath, Samantha L Hocking, Miriam Priglinger, Susan Day, Geoffrey K Herkes, Martin Krause, Gregory R Fulcher
INTRODUCTION: Both hyperglycaemia and hypoglycaemia in acute ischaemic stroke (AIS) are associated with increased infarct size and worse functional outcomes. Thus, therapies that can maintain normoglycaemia during stroke are clinically important. Glucagon-like peptide 1 (GLP-1) analogues, including exenatide, are routinely used in the treatment of hyperglycaemia in type 2 diabetes, but data on the usefulness of this class of agents in the management of elevated glucose levels in AIS are limited...
2016: BMJ Open
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