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Current Diabetes Reviews

Editor-in-Chief

ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

Systematic Review Article

Systematic Review of Glucagon-Like Peptide One Receptor Agonist Liraglutide of Subjects with Heart Failure with Reduced Left Ventricular Ejection Fraction

Author(s): Farah Hamad, Asim Ahmed Elnour*, Abdelgadir Elamin, Sasha Mohamed, Isra Yousif, Judit Don, Semira Abdi, Abdulla Al Amoodi, Ahmed Ibrahim Fathelrahman, Kishore Gnana, Fahad Alanzi, Abubakar B Abubakar, Salma Mohammed Magboul, Sahar Asim Ahmed and Adel Sadeq

Volume 17, Issue 3, 2021

Published on: 21 August, 2020

Page: [280 - 292] Pages: 13

DOI: 10.2174/1573399816999200821164129

Price: $65

Abstract

Background: The major cardiovascular outcome trials on glucagon-like peptide one-receptor agonists have examined its effect on hospitalization of subjects with heart failure; however, very limited trials have been conducted on subjects with reduced left ventricular ejection fraction (r- LVEF) as a primary outcome.

Objective: We have conducted a systematic review of two major (FIGHT and LIVE) placebo-controlled trials of liraglutide and its clinical effect on the ejection fraction of subjects with heart failure.

Methods: Medline data was retrieved for trials involving liraglutide from 2012 to 2020. The inclusion criteria for trials were: subjects with or without type 2 diabetes mellitus (T2DM), subjects with heart failure with rLVEF, major trials (phase II or III) on liraglutide, trials included liraglutide with defined efficacy primary outcome of patients with heart failure with rLVEF. The search was limited to the English language, whereby two trials [FIGHT and LIVE] had been included and two trials were excluded due to different primary outcomes. Participants (541) had been randomized for either liraglutide or placebo for 24 weeks.

Results: In the FIGHT trial the primary intention-to-treat, sensitivity, and diabetes subgroup analyses have shown no significant between-group difference in the global rank scores (mean rank of 146 in the liraglutide group versus 156 in the placebo group; Wilcoxon rank-sum P=.31), number of deaths, re-hospitalizations for heart failure, or the composite of death or change in NT-pro BNP level (P= .94). In the LIVE trial, the change in the left ventricular ejection fraction (LVEF) from baseline to week 24 was not significantly different between treatment groups. The overall discontinuation rate of liraglutide was high in the FIGHT trial (29%, 86) as compared to that in the LIVE trial (11.6%, 28).

Conclusion: FIGHT and LIVE trials have demonstrated that liraglutide use in subjects with heart failure and rLVEF was implicated with an increased adverse risk of heart failure-related outcomes.

Keywords: Glucagon-Like Peptide One Receptor Agonist (GLP-1 RA), Heart Failure (HF), Left Ventricular Ejection Fraction (LVEF), liraglutide, Placebo-Controlled Randomized Clinical Trial (PC-RCT), Randomized Clinical Trial (RCT), reduced Left Ventricular Ejection Fraction (rLVEF).

[1]
Sharma A, Pagidipati NJ, Califf RM, et al. Impact of regulatory guidance on evaluating cardiovascular risk of new glucose-lowering therapies to treat type 2 diabetes mellitus: lessons learned and future directions. Circulation 2020; 141(10): 843-62.
[2]
Sokos GG, Nikolaidis LA, Mankad S, Elahi D, Shannon RP. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail 2006; 12(9): 694-9.
[http://dx.doi.org/10.1016/j.cardfail.2006.08.211] [PMID: 17174230]
[3]
Thrainsdottir I, Malmberg K, Olsson A, Gutniak M, Rydén L. Initial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure. Diab Vasc Dis Res 2004; 1(1): 40-3.
[http://dx.doi.org/10.3132/dvdr.2004.005] [PMID: 16305055]
[4]
Nikolaidis LA, Mankad S, Sokos GG, et al. Effects of glucagon-like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation 2004; 109(8): 962-5.
[http://dx.doi.org/10.1161/01.CIR.0000120505.91348.58] [PMID: 14981009]
[5]
Arturi F, Succurro E, Miceli S, et al. Liraglutide improves cardiac function in patients with type 2 diabetes and chronic heart failure. Endocrine 2017; 57(3): 464-73.
[http://dx.doi.org/10.1007/s12020-016-1166-4] [PMID: 27830456]
[6]
Sharma A, Ambrosy AP, DeVore AD, et al. Liraglutide and weight loss among patients with advanced heart failure and a reduced ejection fraction: insights from the FIGHT trial. ESC Heart Fail 2018; 5(6): 1035-43.
[http://dx.doi.org/10.1002/ehf2.12334] [PMID: 30120812]
[7]
Nyström T. Effects on subclinical heart failure in type 2 diabetic subjects on liraglutide treatment vs. glimepiride both in combination with metformin: A randomized open parallel-group study Front Endocrinol (Lausanne) 2017; 8: 325.
[8]
Margulies KB, Hernandez AF, Redfield MM, et al. NHLBI heart failure clinical research network. effects of liraglutide on clinical stability among patients with advanced heart failure and reduced ejection fraction: A randomized clinical trial. JAMA 2016; 316(5): 500-8.
[http://dx.doi.org/10.1001/jama.2016.10260] [PMID: 27483064]
[9]
Jorsal A, Kistorp C, Holmager P, et al. Effect of liraglutide, a glucagon-like peptide-1 analogue, on left ventricular function in stable chronic heart failure patients with and without diabetes (LIVE)-a multicentre, double-blind, randomised, placebo-controlled trial. Eur J Heart Fail 2017; 19(1): 69-77.
[http://dx.doi.org/10.1002/ejhf.657] [PMID: 27790809]
[10]
Nielsen R, Jorsal A, Iversen P, et al. Heart failure patients with prediabetes and newly diagnosed diabetes display abnormalities in myocardial metabolism. J Nucl Cardiol 2018; 25(1): 169-76.
[http://dx.doi.org/10.1007/s12350-016-0622-0] [PMID: 27473218]
[11]
Stewart LA, Clarke M, Rovers M, et al. PRISMA-IPD Development Group. Preferred Reporting Items for Systematic Review and Meta-Analyses of individual participant data: the PRISMA-IPD Statement. JAMA 2015; 313(16): 1657-65.
[http://dx.doi.org/10.1001/jama.2015.3656] [PMID: 25919529]
[12]
Margulies KB, Anstrom KJ, Hernandez AF, et al. Heart Failure Clinical Research Network. GLP-1 agonist therapy for advanced heart failure with reduced ejection fraction: design and rationale for the functional impact of GLP-1 for heart failure treatment study. Circ Heart Fail 2014; 7(4): 673-9.
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.000346] [PMID: 25028349]
[13]
Jorsal A, Wiggers H, Holmager P, et al. A protocol for a randomised, double-blind, placebo-controlled study of the effect of LIraglutide on left VEntricular function in chronic heart failure patients with and without type 2 diabetes (The LIVE Study). BMJ Open 2014; 4(5): e004885
[http://dx.doi.org/10.1136/bmjopen-2014-004885] [PMID: 24844271]
[14]
Marso SP, Daniels GH, Brown-Frandsen K, et al. LEADER Steering Committee; LEADER Trial Investigators. LEADER Trial Investigators. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016; 375(4): 311-22.
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[15]
Zhang JY, Wang XY, Wang X. Effects of liraglutide on hemodynamic parameters in patients with heart failure. Oncotarget 2017; 8(37): 62693-702.
[http://dx.doi.org/10.18632/oncotarget.18570] [PMID: 28977981]
[16]
Zheng RH, Bai XJ, Zhang WW, et al. Liraglutide attenuates cardiac remodeling and improves heart function after abdominal aortic constriction through blocking angiotensin II type 1 receptor in rats. Drug Des Devel Ther 2019; 13: 2745-57.
[http://dx.doi.org/10.2147/DDDT.S213910] [PMID: 31496651]
[17]
Shiraki A, Oyama JI, Nishikido T, Node K. GLP-1 analog liraglutide-induced cardiac dysfunction due to energetic starvation in heart failure with non-diabetic dilated cardiomyopathy. Cardiovasc Diabetol 2019; 18(1): 164.
[http://dx.doi.org/10.1186/s12933-019-0966-2] [PMID: 31779634]
[18]
Nreu B, Dicembrini I, Tinti F, Sesti G, Mannucci E, Monami M. Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis 2020; 30(7): 1106-14.
[http://dx.doi.org/10.1016/j.numecd.2020.03.013] [PMID: 32448716]
[19]
Redouane B, Greene SJ, Fudim M, et al. Effects of Liraglutide on Worsening Renal Function Among Patients With Heart Failure With Reduced Ejection Fraction: Insights From the FIGHT Trial. Circ Heart Fail 2020; 13(5): e006758
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006758] [PMID: 32362166]
[20]
Liang B, Gu N. Liraglutide in the treatment of heart failure: insight from FIGHT and LIVE. Cardiovasc Diabetol 2020; 19(1): 106.
[http://dx.doi.org/10.1186/s12933-020-01088-3] [PMID: 32631360]

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