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Study · Randomized controlled trial · n = 254 · 2022

1 result

Plasma metabolites associated with functional and clinical outcomes in heart failure with reduced ejection fraction with and without type 2 diabetes.

Lerman JB, Giamberardino SN, Hernandez AF, Felker GM, Shah SH, McGarrah RW

Scientific reports2 Jun 2022Cited by 7 (Europe PMC)

PMID35654972 (opens in a new tab)PMCIDPMC9163122 (opens in a new tab)DOI10.1038/s41598-022-12973-0 (opens in a new tab)PepBankPUB-35654972
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Summary

Heart failure with reduced ejection fraction (HFrEF) is increasingly treated with medications for type 2 diabetes mellitus (T2DM). Whether metabolic derangements in HFrEF and T2DM are associated with differential outcomes remains unclear. Therefore, understanding molecular pathways in HFrEF and T2DM and their effects on clinical endpoints is important. The FIGHT trial randomized 300 individuals with HFrEF and a recent HF hospitalization to liraglutide (a GLP-1 receptor agonist) versus placebo to assess effects on mortality, HF rehospitalization, and 6-month change in NT-ProBNP. Although the trial showed no clinical benefit of liraglutide, the trial population was highly enriched for individuals with T2DM. Sixty metabolites were quantified via mass spectrometry in plasma from 254 FIGHT participants (N = 147 (57.9%) with T2DM). Principal components analysis reduced the high number of correlated metabolites into uncorrelated factors. The association of factor levels with 90-day changes in 6-min walk distance (6MWD) and NT-proBNP, and with time to mortality or HF hospitalization were evaluated. There were no changes in metabolite factors according to treatment assignment. However, in analyses stratified by T2DM status, changes in five plasma metabolite factors correlated with changes in functional outcomes beyond adjustment: factor 2 (branched-chain amino acids [BCAA]) correlated with changes in NT-proBNP (ρ = - 0.291, p = 4 × 10-4) and 6MWD (ρ= 0.265, p = 0.011); factor 1 (medium-chain acylcarnitines;  ρ = 0.220, p = 0.008), factor 4 (long-chain dicarboxylacylcarnitines; ρ = 0.191, p = 0.019), factor 5 (long-chain acylcarnitines; ρ = 0.198, p = 0.017), and factor 8 (urea cycle metabolites; ρ = - 0.239, p = 4 × 10-3), correlated with change in NT-proBNP. Factor 4 was associated with time-to-event (HR = 1.513 [95% CI 1.208-1.896], p = 3 × 10-4) with a trend towards stronger prognostic effect in T2DM (T2DM: p = 1 × 10-3, non-T2DM: p = 0.1). We identified metabolites of BCAA, urea cycle and fatty acid metabolism as biomarkers of HFrEF outcomes, with observed differences in HFrEF patients with T2DM. Such biomarkers might enable future diagnostic or therapeutic interventions in individuals with HFrEF and T2DM.Trial Registration: Clinicaltrials.gov. Identifier: NCT01800968. First posted: February 28, 2013.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study1

1 result from studies that gave the peptide. 1 result from people.

  1. 01HumanRandomized controlled trialMechanism

    In adults with heart failure with reduced ejection fraction in the FIGHT trial, plasma metabolite factors did not change according to liraglutide versus placebo assignment.

    In plain wordsIn adults with heart failure, blood metabolite patterns did not differ between those given liraglutide and those given placebo.

    Peptide
    Liraglutide
    Outcome
    No significant changePlasma metabolite factors by treatment assignment
    Study

    n = 254

    Comparator
    Placebo
    Outcome group
    Metabolic pathways and metabolomics · Cardiovascular
    Studied dose
    Dose not stated

    Source sentences

    Summary
    There were no changes in metabolite factors according to treatment assignment.
    2 context sentences
    Summary · context
    The FIGHT trial randomized 300 individuals with HFrEF and a recent HF hospitalization to liraglutide (a GLP-1 receptor agonist) versus placebo to assess effects on mortality, HF rehospitalization, and 6-month change in NT-ProBNP.
    Summary · context
    Sixty metabolites were quantified via mass spectrometry in plasma from 254 FIGHT participants (N = 147 (57.9%) with T2DM).

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2Results postedNCT01800968

Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT)

Duke Universityn = 300Apr 2013 to Oct 2015

Acute Heart Failure

Trial pageClinicalTrials.govUpdated 15 Feb 2017

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    12 Oct 2026, 11:11 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:05 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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