Design of the liraglutide effect and action in diabetes: Evaluation of cardiovascular outcome results (LEADER) trial

Marso, Steven P.; Poulter, Neil; Nissen, Steven E.; Nauck, Michael A.; Zinman, Bernard; Daniels, Gilbert H.; Pocock, Stuart J.; Steinberg, William M.; Bergenstal, Richard M.; Mann, Johannes F.E.; Ravn, Lisbet; Frandsen, Kirstine Brown; Moses, Alan C.; Buse, John B.

doi:10.1016/j.ahj.2013.07.012

Cited by 190 publications

(169 citation statements)

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“…It hypothesized, adiponectin with its antagonistic effects on TNF-a, may improve diabetes, hypertension, apoptosis, and atherosclerosis [35]. The Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial showed conclusive data regarding the cardiovascular safety of liraglutide relative to standard of care for a global population of patients with T2DM [36].…”

Section: Discussionmentioning

confidence: 99%

Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Mazidi

Karimi

Rezaie

et al. 2017

Journal of Diabetes and its Complications

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Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials Article (Accepted Version) http://sro.sussex.ac.uk Mazidi, Mohsen, Karimi, Ehsan, Rezaie, Peyman and Ferns, Gordon A (2016) Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Journal of Diabetes and its Complications. ISSN 1056-8727 This version is available from Sussex Research Online: http://sro.sussex.ac.uk/61270/ This document is made available in accordance with publisher policies and may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the URL above for details on accessing the published version. Copyright and reuse:Sussex Research Online is a digital repository of the research output of the University.Copyright and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable, the material made available in SRO has been checked for eligibility before being made available.Copies of full text items generally can be reproduced, displayed or performed and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. methods were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. Heterogeneity was quantitatively assessed using the I 2 index. Random effects meta-regression was performed using unrestricted maximum likelihood method to evaluate the impact of potential moderator. ÔØ Å ÒÙ×Ö ÔØ A C C E P T E DInternational Prospective Register for Systematic Reviews (PROSPERO) number CRD42016036868.Results: Meta-analysis of the data from 7 treatment arms revealed a significant reduction in serum CRP concentrations following treatment with GLP-1 RAs (WMD -2.14 (mg/dL), 95% CI -3.51, -0.78, P=0.002; I 2 96.1%). Removal of one study in the meta-analysis did not change the result in the sensitivity analysis (WMD -2.14(mg/dL), 95% CI -3.51, -0.78, P=0.002; I 2 96.1%), indicating that our results could not be solel...

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Section: Discussionmentioning

confidence: 99%

Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Mazidi

Karimi

Rezaie

et al. 2017

Journal of Diabetes and its Complications

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“…7 Recently, liraglutide has been suggested to be beneficial for MI, independent of glycemic control. 7,8 In fact, the therapeutic benefits of liraglutide have been reported in several studies, including improved cardiac performance, 9 an attenuated infarct size, 10 increased myocardial blood flow, 11 inhibition of myocardial apoptosis 12 and activation of myocardial signaling pathways. 13 Furthermore, the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial, a randomized, double-blind, placebo-controlled clinical trial with long-term follow-up, confirmed the favorable effects of liraglutide on MI.…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Qi¹,

Lü

Li³

et al. 2017

IJN

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The local, intramyocardial injection of proteins into the infarcted heart is an attractive option to initiate cardiac regeneration after myocardial infarction (MI). Liraglutide, which was developed as a treatment for type 2 diabetes, has been implicated as one of the most promising protein candidates in cardiac regeneration. A significant challenge to the therapeutic use of this protein is its short half-life in vivo. In this study, we evaluated the therapeutic effects and long-term retention of liraglutide loaded in poly(lactic- co -glycolic acid)–poly(ethylene glycol) (PLGA–PEG) nanoparticles (NP-liraglutide) on experimental MI. PLGA–PEG nanoparticles (NPs) have been shown to efficiently load liraglutide and release bioactive liraglutide in a sustained manner. For in vitro test, the released liraglutide retained bioactivity, as measured by its ability to activate liraglutide signaling pathways. Next, we compared the effects of an intramyocardial injection of saline, empty NPs, free liraglutide and NP-liraglutide in a rat model of MI. NPs were detected in the myocardium for up to 4 weeks. More importantly, an intramyocardial injection of NP-liraglutide was sufficient to improve cardiac function ( P <0.05), attenuate the infarct size ( P <0.05), preserve wall thickness ( P <0.05), promote angiogenesis ( P <0.05) and prevent cardiomyocyte apoptosis ( P <0.05) at 4 weeks after injection without affecting glucose levels. The local, controlled, intramyocardial delivery of NP-liraglutide represents an effective and promising strategy for the treatment of MI.

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“…Over the next years, with several CV outcome trials due to report (Figure 1) [22][23][24][25][26][27][28][29] , an opportunity for great learnings is at our doorsteps. Since some trials might even contribute to paradigm shifts in our approach to T2D management, it is important to contextualize the results to the study populations in scope taking into account T2D disease duration, degree of vasculopathy, duration of the intervention, and the mode of action of the intervention (Figure 2).…”

Section: Results Of CV Outcome Trials In T2d Need To Be Interpreted Imentioning

confidence: 99%

Interpretation of cardiovascular outcome trials in type 2 diabetes needs a multiaxial approach

Johansen¹

2015

WJD

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Design of the liraglutide effect and action in diabetes: Evaluation of cardiovascular outcome results (LEADER) trial

Cited by 190 publications

References 18 publications

Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Treatment with GLP1 receptor agonists reduce serum CRP concentrations in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Spatiotemporal delivery of nanoformulated liraglutide for cardiac regeneration after myocardial infarction

Interpretation of cardiovascular outcome trials in type 2 diabetes needs a multiaxial approach

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