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Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study

  • Original Article
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Journal of Nuclear Cardiology Aims and scope

Abstract

Background

The glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR).

Methods and Results

CHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT) and changes in MBF and MFR from baseline to follow-up were measured quantitatively by 18F-FDG and 15O-H2O positron emission tomography. Compared with placebo, liraglutide reduced weight (P = 0.03), HbA1c (P = 0.03) and the 2-hour glucose value during the OGTT (P = 0.004). Despite this, changes in MGU (P = 0.98), MBF (P = 0.76) and MFR (P = 0.89) from baseline to follow-up did not differ between groups. Furthermore, there was no association between the level of insulin resistance at baseline and changes in MGU in patients treated with liraglutide.

Conclusion

Liraglutide did not affect MGU, MBF, or MFR in non-diabetic CHF patients. Any potential increase in cardiac events in these patients seems not to involve changes in MGU, MBF, or MFR.

Trial Registration

Trial registry: http://www.ClinicalTrials.org. Identifier: NCT01472640. Url: https://clinicaltrials.gov/ct2/show/NCT01472640?term=NCT01472640&rank=1

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Abbreviations

CHF:

Chronic heart failure

HEC:

Hyperinsulinemic-euglycemic clamp

LVEF:

Left ventricular ejection fraction

MGU:

Myocardial glucose uptake

MBF:

Myocardial blood flow

MFR:

Myocardial flow reserve

OGTT:

Oral glucose tolerance test

PTI:

Perfusable tissue index

WMS:

Wall motion score

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Disclosures

Anders Jorsal and Lise Tarnow hold shares in Novo Nordisk A/S. Caroline Kistorp has been a principal or sub-investigator for the following companies: MSD, Novo Nordisk, Novartis, GSK and Astra Zeneca, and has participated in advisory boards for MSD and Astra Zeneca and Novo Nordisk. Henrik Wiggers has been a principal or sub-investigator in studies involving the following pharmaceutical companies: MSD, Bayer, Daiichi-Sankyo, Novartis, Novo Nordisk, Sanofi-Aventis and Pfizer. Ida Gustafsson has been principal or sub-investigator in studies involving the following pharmaceutical companies: Novartis, Janssen, GSK, MSD and Astra-Zeneca and has participated in an advisory board meeting at Boehringer-Ingelheim and Novo Nordisk. Lise Tarnow has conducted studies with, served as a consultant for and is a member of advisory boards for Novo Nordisk. The authors declare no other conflicts of interests.

Author information

Authors and Affiliations

  1. Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark

    Roni Nielsen MD, PhD, Anders Jorsal MD, PhD, Hans Erik Bøtker MD, DMSc & Henrik Wiggers MD, DMSc

  2. Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark

    Anders Jorsal MD, PhD & Henrik Wiggers MD, DMSc

  3. Department of Nuclear Medicine & PET Centre, Aarhus University Hospital, Aarhus, Denmark

    Peter Iversen MD, PhD, Lars Poulsen Tolbod MSc, PhD, Kirsten Bouchelouche MD, DMSc, Jens Sørensen MD, DMSc & Hendrik Johannes Harms MSc, PhD

  4. Faculty of Health, Aarhus University, Aarhus, Denmark

    Allan Flyvbjerg MD, DMSc

  5. Steno Diabetes Center, Gentofte, Denmark

    Lise Tarnow MD, DMSc

  6. Department of Endocrinology and Internal Medicine, Herlev University Hospital, Copenhagen, Denmark

    Caroline Kistorp MD, PhD

  7. Department of Cardiology, Hvidovre University Hospital, Copenhagen, Denmark

    Ida Gustafsson MD, PhD

Authors
  1. Roni Nielsen MD, PhD
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  2. Anders Jorsal MD, PhD
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  4. Lars Poulsen Tolbod MSc, PhD
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  5. Kirsten Bouchelouche MD, DMSc
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  6. Jens Sørensen MD, DMSc
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  7. Hendrik Johannes Harms MSc, PhD
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  8. Allan Flyvbjerg MD, DMSc
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  9. Lise Tarnow MD, DMSc
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  10. Caroline Kistorp MD, PhD
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  11. Ida Gustafsson MD, PhD
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  12. Hans Erik Bøtker MD, DMSc
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  13. Henrik Wiggers MD, DMSc
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Corresponding author

Correspondence to Roni Nielsen MD, PhD.

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Funding

The study was investigator-initiated and investigator-designed. The investigators received an unrestricted grant from Novo Nordisk A/S for the LIVE study, but the company was not involved in data collection, study management, analysis, or interpretation of data; nor in preparation, approval and the decision to submit the present manuscript.

All editorial decisions for this article, including selection of reviewers and the final decision, were made by guest editor Robert Gropler, MD

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Nielsen, R., Jorsal, A., Iversen, P. et al. Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study. J. Nucl. Cardiol. 26, 585–597 (2019). https://doi.org/10.1007/s12350-017-1000-2

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  • DOI: https://doi.org/10.1007/s12350-017-1000-2

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