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https://www.readbyqxmd.com/read/28914987/diabetes-news
#1
Ann M Carracher, Payal H Marathe, Kelly L Close
More than 31,000 attendeesfrom around the world gathered in Barcelona, Spain for the 2017 European Society of Cardiology conference. In presentinga post-hoc analysis of the Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes(LEADER)(1) trial, Dr Neil Poulter (Imperial College London, UK) showedthat results are still positive, indicating cardioprotection, after adjusting for baseline history of stroke or myocardial infarction (MI), which had no mediating effect on the significant association between Novo Nordisk's (Copenhagen, Denmark) glucagon-like peptide-1 (GLP-1) agonist Victoza (liraglutide) and cardiovascular risk reduction...
September 15, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#2
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28871349/recent-insights-into-pharmacologic-cardiovascular-risk-reduction-in-type-2-diabetes-mellitus
#3
Scott L Purga, Mandeep Sidhu, Michael Farkouh, Joshua Schulman-Marcus
Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension...
September 4, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28772063/the-%C3%AF-3-fatty-acid-%C3%AE-linolenic-acid-extends-caenorhabditis-elegans-lifespan-via-nhr-49-ppar%C3%AE-and-oxidation-to-oxylipins
#4
Wenbo Qi, Gloria E Gutierrez, Xiaoli Gao, Hong Dixon, Joe A McDonough, Ann M Marini, Alfred L Fisher
The dietary intake of ω-3 polyunsaturated fatty acids has been linked to a reduction in the incidence of aging-associated disease including cardiovascular disease and stroke. Additionally, long-lived Caenorhabditis elegans glp-1 germ line-less mutant animals show a number of changes in lipid metabolism including the increased production of the ω-3 fatty acid, α-linolenic acid (ALA). Here, we show that the treatment of C. elegans with ALA produces a dose-dependent increase in lifespan. The increased longevity of the glp-1 mutant animals is known to be dependent on both the NHR-49/PPARα and SKN-1/Nrf2 transcription factors, although the mechanisms involved are incompletely understood...
October 2017: Aging Cell
https://www.readbyqxmd.com/read/28533296/glp-1r-as-a-target-for-the-treatment-of-diabetic-retinopathy-friend-or-foe
#5
REVIEW
Rafael Simó, Cristina Hernández
Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results-A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published...
June 2017: Diabetes
https://www.readbyqxmd.com/read/28522196/impact-of-glucose-lowering-therapies-on-risk-of-stroke-in-type-2-diabetes
#6
REVIEW
F Bonnet, A J Scheen
Patients with type 2 diabetes (T2D) have an increased risk of stroke compared with people without diabetes. However, the effects of glucose-lowering drugs on risk of ischaemic stroke in T2D have been less extensively investigated than in coronary heart disease. Some evidence, including the UKPDS, has suggested a reduced risk of stroke with metformin, although the number of studies is limited. Inhibition of the KATP channels increases ischaemic brain lesions in animals. This is in agreement with a recent meta-analysis showing an increased risk of stroke with sulphonylureas vs...
May 15, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28501352/effects-of-glucagon-like-peptide-1-receptor-agonists-on-mortality-and-cardiovascular-events-a-comprehensive-meta-analysis-of-randomized-controlled-trials
#7
Matteo Monami, Stefania Zannoni, Laura Pala, Antonio Silverii, Francesco Andreozzi, Giorgio Sesti, Edoardo Mannucci
INTRODUCTION: The publication of the results of LEADER and SUSTAIN-6 trials suggested a possible beneficial effect of the class of GLP-1 receptor agonists on cardiovascular morbidity and mortality. The aim of the present meta-analysis is to collect and synthetize all available evidence on the effect of GLP-1 receptor agonists on cardiovascular events and mortality. METHODS: A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration >11weeks, enrolling patients with type 2 diabetes, and comparing a GLP-1 receptor agonist with placebo or any other non-GLP-1 receptor agonist drug...
August 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28489279/dipeptidyl-peptidase-dpp-4-inhibitors-and-glucagon-like-peptide-glp-1-analogues-for-prevention-or-delay-of-type-2-diabetes-mellitus-and-its-associated-complications-in-people-at-increased-risk-for-the-development-of-type-2-diabetes-mellitus
#8
REVIEW
Bianca Hemmingsen, David P Sonne, Maria-Inti Metzendorf, Bernd Richter
BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. OBJECTIVES: To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these...
May 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28454792/baseline-characteristics-of-patients-enrolled-in-the-exenatide-study-of-cardiovascular-event-lowering-exscel
#9
RANDOMIZED CONTROLLED TRIAL
Robert J Mentz, M Angelyn Bethel, Stephanie Gustavson, Vivian P Thompson, Neha J Pagidipati, John B Buse, Juliana C Chan, Nayyar Iqbal, Aldo P Maggioni, Steve P Marso, Peter Ohman, Neil Poulter, Ambady Ramachandran, Bernard Zinman, Adrian F Hernandez, Rury R Holman
BACKGROUND: EXSCEL is a randomized, double-blind, placebo-controlled trial examining the effect of exenatide once-weekly (EQW) versus placebo on time to the primary composite outcome (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke) in patients with type 2 diabetes mellitus (DM) and a wide range of cardiovascular (CV) risk. METHODS: Patients were enrolled at 688 sites in 35 countries. We describe their baseline characteristics according to prior CV event status and compare patients with those enrolled in prior glucagon-like peptide-1 receptor agonist (GLP-1RA) outcomes trials...
May 2017: American Heart Journal
https://www.readbyqxmd.com/read/28440199/anti-hyperglycemic-agents-for-the-treatment-of-type-2-diabetes-mellitus-role-in-cardioprotection-during-the-last-decade
#10
Duygu Kocyigit, Kadri Murat Gurses, Muhammed Ulvi Yalcin, Lale Tokgozoglu
Type 2 diabetic patients are known to have a tendency to develop cardiovascular (CV) disease (CVD), and related unfavourable outcomes such as heart failure, myocardial infarction (MI), cerebrovascular events (e.g. stroke), and related mortality. Long- term clinical trials have revealed contradictory findings regarding the relationship between glycemic control and CV benefits due to variations in the key characteristics of the study population. During the last decade, number of pharmacological agents used for glucose- lowering in the treatment of type 2 diabetes mellitus (T2DM) has increased owing to the introduction of dipeptidyl peptidase- IV (DPP- IV) inhibitors, glucagon- like peptide- 1 (GLP- 1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT- 2) inhibitors...
2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28431669/after-the-leader-trial-and-sustain-6-how-do-we-explain-the-cardiovascular-benefits-of-some-glp-1-receptor-agonists
#11
B Vergès, B Charbonnel
Recent cardiovascular outcome trials - the LEADER with liragutide and SUSTAIN-6 with semaglutide - have shown significant reductions of major cardiovascular (CV) events with these glucagon-like peptide (GLP)-1 receptor agonists. Progressive separation of the treatment and placebo curves, starting clearly between 12 and 18 months of the trial period, and significant reductions in the risk of myocardial infarction and stroke, indicate that the beneficial CV effects observed with GLP-1 receptor agonists could be due to an antiatherogenic effect...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28407414/association-of-glucagon-like-peptide-1-receptor-agonist-use-and-rates-of-acute-myocardial-infarction-stroke-and-overall-mortality-in-patients-with-type-2-diabetes-mellitus-in-a-large-integrated-health-system
#12
Robert S Zimmerman, Todd M Hobbs, Brian J Wells, Sheldon X Kong, Michael W Kattan, Jon Bouchard, Kevin M Chagin, Changhong Yu, Brian Sakurada, Alex Milinovich, Wayne Weng, Janine M Bauman, Kevin M Pantalone
AIMS: To assess the potential impact of glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure on cardiovascular disease (CVD) and mortality outcomes in patients with type 2 diabetes (T2D), using a large retrospective cohort. RESEARCH DESIGN AND METHODS: Patients who had T2D between 2005 and 2014 (N = 105 862) were identified from the electronic health record system at Cleveland Clinic using a validated electronic phenotype. A time-dependent, Cox, multiple regression analysis was used to assess the association between GLP-1RA exposure and risk of acute myocardial infarction (AMI), stroke/cerebrovascular accident (CVA), and overall mortality, as well as the composite of all three outcomes...
April 13, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28249585/incretin-based-agents-in-type-2-diabetic-patients-at-cardiovascular-risk-compare-the-effect-of-glp-1-agonists-and-dpp-4-inhibitors-on-cardiovascular-and-pancreatic-outcomes
#13
Zeqing Zhang, Xi Chen, Puhan Lu, Jianhua Zhang, Yongping Xu, Wentao He, Mengni Li, Shujun Zhang, Jing Jia, Shiying Shao, Junhui Xie, Yan Yang, Xuefeng Yu
BACKGROUND: Incretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk. METHODS: Six prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia...
March 1, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28235974/acute-effects-of-glucagon-like-peptide-1-glp-19-36-amide-and-exenatide-on-mesenteric-blood-flow-cardiovascular-parameters-and-biomarkers-in-healthy-volunteers
#14
Lasse Bremholm, Ulrik B Andersen, Mads Hornum, Linda Hilsted, Simon Veedfald, Bolette Hartmann, Jens Juul Holst
Glucagon-like peptide-1 (GLP-1, GLP-17-36amide) and its sister peptide glucagon-like peptide 2 (GLP-2) influence numerous intestinal functions and GLP-2 greatly increases intestinal blood flow. We hypothesized that GLP-1 also stimulates intestinal blood flow and that this would impact on the overall digestive and cardiovascular effects of the hormone. To investigate the influence of GLP-1 receptor agonism on mesenteric and renal blood flow and cardiovascular parameters, we carried out a double-blinded randomized clinical trial...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28151519/-results-of-the-leader-study-current-evidence-and-perspectives-in-research
#15
Edoardo Mannucci
The LEADER study is a trial performed to demonstrate the cardiovascular safety of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. The study was performed on patients with type 2 diabetes and high cardiovascular risk, mostly with prior cardiovascular events. Although the primary goal was the demonstration of non-inferiority versus placebo, the LEADER study revealed a significant reduction of the overall incidence of major cardiovascular events, as well as a reduction of all-cause and cardiovascular mortality...
December 2016: Giornale Italiano di Cardiologia
https://www.readbyqxmd.com/read/28122257/delayed-administration-of-the-glp-1-receptor-agonist-liraglutide-improves-metabolic-and-functional-recovery-after-cerebral-ischemia-in-rats
#16
Wenbin Dong, Yunping Miao, Aiying Chen, Min Cheng, Xiaodi Ye, Fahuan Song, Gaoli Zheng
Glucagon-like peptide 1 receptor (GLP-1R) agonists administered before or immediately after induction of experimental stroke have been shown to provide acute neuroprotection. Here, we determined whether delayed treatment with a GLP-1R agonist could improve metabolic and functional recovery after stroke. Rats were subjected to middle cerebral artery occlusion (MCAO) and given the well-established GLP-1R agonist liraglutide (50, 100, or 200μg/kg) or normal saline (NS) daily for 4 weeks, starting 1 day after MCAO...
February 22, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/27865185/a-new-era-in-the-management-of-type-2-diabetes-is-cardioprotection-at-long-last-a-reality
#17
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...
February 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27863704/cardiovascular-effects-of-glucose-lowering-therapies-for-type-2-diabetes-new-drugs-in-perspective
#18
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...
May 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/27862902/cardiovascular-events-and-all-cause-mortality-associated-with-sulphonylureas-compared-with-other-antihyperglycaemic-drugs-a-bayesian-meta-analysis-of-survival-data
#19
Steve Bain, Eric Druyts, Chakrapani Balijepalli, Carl A Baxter, Craig J Currie, Romita Das, Richard Donnelly, Kamlesh Khunti, Haya Langerman, Paul Leigh, Gaye Siliman, Kristian Thorlund, Kabirraaj Toor, Jiten Vora, Edward J Mills
AIM: To conduct a systematic review and meta-analysis to determine the risk of cardiovascular events and all-cause mortality associated with sulphonylureas (SUs) vs other glucose lowering drugs in patients with T2DM (T2DM). MATERIALS AND METHODS: A systematic review of Medline, Embase, Cochrane and clinicaltrials.gov was conducted for studies comparing SUs with placebo or other antihyperglycaemic drugs in patients with T2DM. A cloglog model was used in the Bayesian framework to obtain comparative hazard ratios (HRs) for the different interventions...
March 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27856285/neurotrophic-and-neuroprotective-effects-of-oxyntomodulin-in-neuronal-cells-and-a-rat-model-of-stroke
#20
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...
February 2017: Experimental Neurology
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