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).
[http://dx.doi.org/10.1016/j.cardfail.2006.08.211] [PMID: 17174230]
[http://dx.doi.org/10.3132/dvdr.2004.005] [PMID: 16305055]
[http://dx.doi.org/10.1161/01.CIR.0000120505.91348.58] [PMID: 14981009]
[http://dx.doi.org/10.1007/s12020-016-1166-4] [PMID: 27830456]
[http://dx.doi.org/10.1002/ehf2.12334] [PMID: 30120812]
[http://dx.doi.org/10.1001/jama.2016.10260] [PMID: 27483064]
[http://dx.doi.org/10.1002/ejhf.657] [PMID: 27790809]
[http://dx.doi.org/10.1007/s12350-016-0622-0] [PMID: 27473218]
[http://dx.doi.org/10.1001/jama.2015.3656] [PMID: 25919529]
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.114.000346] [PMID: 25028349]
[http://dx.doi.org/10.1136/bmjopen-2014-004885] [PMID: 24844271]
[http://dx.doi.org/10.1056/NEJMoa1603827] [PMID: 27295427]
[http://dx.doi.org/10.18632/oncotarget.18570] [PMID: 28977981]
[http://dx.doi.org/10.2147/DDDT.S213910] [PMID: 31496651]
[http://dx.doi.org/10.1186/s12933-019-0966-2] [PMID: 31779634]
[http://dx.doi.org/10.1016/j.numecd.2020.03.013] [PMID: 32448716]
[http://dx.doi.org/10.1161/CIRCHEARTFAILURE.119.006758] [PMID: 32362166]
[http://dx.doi.org/10.1186/s12933-020-01088-3] [PMID: 32631360]