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
Open accessAbstract
Aims: To determine the effect of the glucagon-like peptide-1 analogue liraglutide on left ventricular function in chronic heart failure patients with and without type 2 diabetes. Methods and results: LIVE was an investigator-initiated, randomised, double-blinded, placebo-controlled multicentre trial. Patients (n = 241) with reduced left ventricular ejection fraction (LVEF ≤45%) were recruited (February 2012 to August 2015). Patients were clinically stable and on optimal heart failure treatment. Intervention was liraglutide 1.8 mg once daily or matching placebo for 24 weeks. The LVEF was similar at baseline in the liraglutide and the placebo group (33.7 ± 7.6% vs. 35.4 ± 9.4%). Change in LVEF did not differ between the liraglutide and the placebo group; mean difference (95% confidence interval) was −0.8% (−2.1, 0.5; P = 0.24). Heart rate increased with liraglutide [mean difference: 7 b.p.m. (5, 9), P < 0.0001]. Serious cardiac events were seen in 12 (10%) patients treated with liraglutide compared with 3 (3%) patients in the placebo group (P = 0.04). Conclusion: Liraglutide did not affect left ventricular systolic function compared with placebo in stable chronic heart failure patients with and without diabetes. Treatment with liraglutide was associated with an increase in heart rate and more serious cardiac adverse events, and this raises some concern with respect to the use of liraglutide in patients with chronic heart failure and reduced left ventricular function. More data on the safety of liraglutide in different subgroups of heart failure patients are needed.
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In earlier smaller studies with liraglutide in patients with heart failure with reduced left ventricular ejection fraction, the GLP-1RA was associated with increased incidence of serious cardiac events (rhythm disorders, worsening of heart failure).
“in earlier smaller studies with liraglutide in patients with HF with reduced left ventricular ejection fraction, the GLP-1RA was associated with increased incidence of serious cardiac events (rhythm disorders, worsening of HF)”
From Safety of Semaglutide (2021) · cites this paper as [103]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredA small randomized study evaluating 12 weeks of albiglutide versus placebo in patients with HFrEF showed no significant differences in LVEF, 6-minute walk test, myocardial glucose utilization, or oxygen use.
“No significant differences were seen in LVEF, 6 min walk test, myocardial glucose utilization, or oxygen use.550”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [550]
The small randomized study of albiglutide in HFrEF was too small and too short to evaluate clinical outcomes.
“The study was too small and too short to evaluate clinical outcomes.”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [550]
Two small randomized clinical trials of liraglutide in patients with heart failure with reduced ejection fraction suggested potential harm of liraglutide, although neither trial found statistically significant differences.
“Furthermore, 2 small randomized clinical trials of liraglutide in patients with HF with reduced EF, 1 of which enrolled patients with recent HF hospitalization, suggested potential harm of liraglutide, although neither trial found statistically significant differences.36,37”
From Use of Glucagon-Like Peptide-1 Receptor Agonists in Patients With Type 2 Diabetes and Cardiovascular Disease: A Review (2020) · cites this paper as [37]
In the LIVE trial, in patients with stable HFrEF, with and without T2DM, there were no significant changes in left ventricular ejection fraction between patients randomized on liraglutide or placebo.
“I nt h eL I V Et r i a l ,i np a t i e n t sw i t hs t a b l eH F r E F ,w i t ha n dw i t hout T2DM, there were no significant changes in left ventricular ejection fraction between patients randomized on liraglutide or placebo.180”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [180]
In the LIVE trial, there was a significant increase in heart rate (P<0.0001) and more serious cardiac adverse events with liraglutide (P=0.04).
“However, there was a significant increase in heart rate (P<0.0001) and more serious cardiac adverse events with liraglutide (P=0.04).”
From Type 2 diabetes mellitus and heart failure: A position statement from the Heart Failure Association of the European Society of Cardiology (2018) · cites this paper as [180]
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- Authors
- Jorsal, A., Kistorp, C., Holmager, P., Tougaard, R. S., Nielsen, R., Hänselmann, A., Nilsson, B., Møller, J. E., Hjort, J., Rasmussen, J., Boesgaard, T. W., Schou, M., Videbæk, L., Gustafsson, I., Flyvbjerg, A., Wiggers, H., & Tarnow, L.
- Affiliations
- Aarhus University (DK)
- University of Copenhagen (DK)
- Herlev Hospital (DK)
- Odense University Hospital (DK)
- Hvidovre Hospital (DK)
- Steno Diabetes Center , Gentofte ,
- Corresponding author
- Jorsal, Anders
- ORCID
- Venue
- European Journal of Heart Failure
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-10-28
- Volume
- 19
- Issue
- 1
- Pages
- 69-77
- ISSN
- 1388-9842 (ISSN-L)
- 1879-0844
- OpenAlex
- W2542456927
- Cited by
- 592
- References
- 30
- Citations by year
- 2026: 84 · 2025: 97 · 2024: 73 · 2023: 55 · 2022: 43 · 2021: 48 · 2020: 48 · 2019: 68 · 2018: 43 · 2017: 31 · 2016: 1 · 2014: 1
- FWCI
- 39.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Heart Failure (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Scopus (Elsevier) (submittedVersion)
- Funders
- Bayer
- Sanofi-Aventis
- Daiichi-Sankyo
- Novo Nordisk
- Novartis
- Pfizer
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- liraglutide, glucagon-like peptide-1 analogues, chronic heart failure, left ventricular ejection fraction, left ventricular systolic function, type 2 diabetes, heart rate, adverse cardiac events, GLP-1 receptor agonists
- MeSH terms
- Liraglutide, Walk Test, Aged, Atrial Fibrillation, Chronic Disease, Diabetes Mellitus, Type 2, Double-Blind Method, Echocardiography, Female, Heart Failure, Heart Rate, Humans, Male, Middle Aged, Peptide Fragments, Stroke Volume, Ventricular Function, Left, Treatment Outcome, Tachycardia, Ventricular, Disease Progression, Natriuretic Peptide, Brain, Acute Coronary Syndrome, Incretins
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