Ceramides are decreased after liraglutide treatment in people with type 2 diabetes: a post hoc analysis of two randomized clinical trials

Background Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide has been shown to induce beneficial changes in the lipid profile and reduce the risk of...

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Published in:Lipids in health and disease Vol. 22; no. 1; pp. 1 - 12
Main Authors: Wretlind, Asger, Curovic, Viktor Rotbain, de Zawadzki, Andressa, Suvitaival, Tommi, Xu, Jin, Zobel, Emilie Hein, von Scholten, Bernt Johan, Ripa, Rasmus Sejersten, Kjaer, Andreas, Hansen, Tine Willum, Vilsbøll, Tina, Vestergaard, Henrik, Rossing, Peter, Legido-Quigley, Cristina
Format: Journal Article
Language:English
Published: London BioMed Central 26.09.2023
BioMed Central Ltd
Springer Nature B.V
BMC
Subjects:
Analysis
Antidiabetics
Biomedical and Life Sciences
Calibration
Cardiovascular disease
Cardiovascular diseases
Care and treatment
Ceramide
Ceramides
Cholesterol, LDL
Clinical Nutrition
Clinical trials
Development and progression
Diabetes
Diabetes mellitus (non-insulin dependent)
Dosage and administration
Drug therapy
Gastrointestinal surgery
GLP-1 receptor agonists
Glucagon
Glucagon-like peptide 1
Health aspects
Insulin resistance
Life Sciences
Lipidology
Lipids
Liquid chromatography
Liraglutide
Mass spectrometry
Mass spectroscopy
Measurement
Medical Biochemistry
Placebos
Plasma
Precision medicine
Scientific imaging
Statistical analysis
Type 2 diabetes
Denmark
Type 2 diabetes
Ceramide
Cardiovascular disease
Liraglutide
ISSN:1476-511X, 1476-511X
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Summary:Background Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide has been shown to induce beneficial changes in the lipid profile and reduce the risk of CVD. Reducing lipotoxic lipids with an antidiabetic drug therapy could be a path towards precision medicine approaches for the treatment of complications to diabetes. In this post-hoc study, an investigation was carried out on the effect of liraglutide on CVD-risk associated ceramides in two randomized clinical trials including participants with type 2 diabetes (T2D). Methods This study analyzed plasma samples from two independent randomized placebo-controlled clinical trials. The first trial, Antiproteinuric Effects of Liraglutide Treatment (LirAlbu12) followed a crossover design where 27 participants were treated for 12 weeks with either liraglutide (1.8 mg/d) or placebo, followed by a four-week washout period, and then another 12 weeks of the other treatment. The second clinical trial, Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LiraFlame26), lasted for 26 weeks and followed a parallel design, where 102 participants were randomized 1:1 to either liraglutide or placebo. Heresix prespecified plasma ceramides were measured using liquid chromatography mass spectrometry and assessed their changes using linear mixed models. Possible confounders were assessed with mediation analyses. Results In the LiraFlame26 trial, 26-week treatment with liraglutide resulted in a significant reduction of two ceramides associated with CVD risk, C16 Cer and C24:1 Cer ( p  < 0.05) compared to placebo. None of the remaining ceramides showed statistically significant changes in response to liraglutide treatment compared to placebo. Significant changes in ceramides were not found after 12-weeks of liraglutide treatment in the LirAlbu12 trial. Mediation analyses showed that weight loss did not affect ceramide reduction. Conclusions It was demonstrated that treatment with liraglutide resulted in a reduction in C16 Cer and C24:1 Cer after 26 weeks of treatment. These findings suggest the GLP-1RA can be used to modulate ceramides in addition to its other properties. Trial registration Clinicaltrial.gov identifier: NCT02545738 and NCT03449654.
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ISSN:1476-511X
1476-511X
DOI:10.1186/s12944-023-01922-z