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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| Vydáno v: | Lipids in health and disease Ročník 22; číslo 1; s. 1 - 12 |
|---|---|
| Hlavní autoři: | , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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London
BioMed Central
26.09.2023
BioMed Central Ltd Springer Nature B.V BMC |
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| ISSN: | 1476-511X, 1476-511X |
| On-line přístup: | Získat plný text |
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| Abstract | 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. |
|---|---|
| AbstractList | 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).BACKGROUNDSpecific 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).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.METHODSThis 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.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.RESULTSIn 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.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.CONCLUSIONSIt 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.Clinicaltrial.gov identifier: NCT02545738 and NCT03449654.TRIAL REGISTRATIONClinicaltrial.gov identifier: NCT02545738 and NCT03449654. 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. Keywords: Cardiovascular disease, Ceramide, Liraglutide, Type 2 diabetes Abstract 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. 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). 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. 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. 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. 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. BackgroundSpecific 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).MethodsThis 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.ResultsIn 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.ConclusionsIt 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 registrationClinicaltrial.gov identifier: NCT02545738 and NCT03449654. |
| ArticleNumber | 160 |
| Audience | Academic |
| Author | Ripa, Rasmus Sejersten Wretlind, Asger von Scholten, Bernt Johan Curovic, Viktor Rotbain Hansen, Tine Willum de Zawadzki, Andressa Legido-Quigley, Cristina Vestergaard, Henrik Xu, Jin Zobel, Emilie Hein Vilsbøll, Tina Kjaer, Andreas Rossing, Peter Suvitaival, Tommi |
| Author_xml | – sequence: 1 givenname: Asger surname: Wretlind fullname: Wretlind, Asger organization: Steno Diabetes Center Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen – sequence: 2 givenname: Viktor Rotbain surname: Curovic fullname: Curovic, Viktor Rotbain organization: Steno Diabetes Center Copenhagen – sequence: 3 givenname: Andressa surname: de Zawadzki fullname: de Zawadzki, Andressa organization: Steno Diabetes Center Copenhagen – sequence: 4 givenname: Tommi surname: Suvitaival fullname: Suvitaival, Tommi organization: Steno Diabetes Center Copenhagen – sequence: 5 givenname: Jin surname: Xu fullname: Xu, Jin organization: King’s College London – sequence: 6 givenname: Emilie Hein surname: Zobel fullname: Zobel, Emilie Hein organization: Steno Diabetes Center Copenhagen, Novo Nordisk A/S – sequence: 7 givenname: Bernt Johan surname: von Scholten fullname: von Scholten, Bernt Johan organization: Steno Diabetes Center Copenhagen, Novo Nordisk A/S – sequence: 8 givenname: Rasmus Sejersten surname: Ripa fullname: Ripa, Rasmus Sejersten organization: Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital – Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen – sequence: 9 givenname: Andreas surname: Kjaer fullname: Kjaer, Andreas organization: Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital – Rigshospitalet & Department of Biomedical Sciences, University of Copenhagen – sequence: 10 givenname: Tine Willum surname: Hansen fullname: Hansen, Tine Willum organization: Steno Diabetes Center Copenhagen – sequence: 11 givenname: Tina surname: Vilsbøll fullname: Vilsbøll, Tina organization: Steno Diabetes Center Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen – sequence: 12 givenname: Henrik surname: Vestergaard fullname: Vestergaard, Henrik organization: Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Department of Medicine, Bornholms Hospital – sequence: 13 givenname: Peter surname: Rossing fullname: Rossing, Peter email: peter.rossing@regionh.dk organization: Steno Diabetes Center Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen – sequence: 14 givenname: Cristina surname: Legido-Quigley fullname: Legido-Quigley, Cristina email: cristina.legido.quigley@regionh.dk organization: Steno Diabetes Center Copenhagen, King’s College London |
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| CitedBy_id | crossref_primary_10_1016_j_jlr_2024_100726 crossref_primary_10_1007_s11886_024_02023_8 crossref_primary_10_1038_s41591_024_03279_x crossref_primary_10_1002_oby_24156 crossref_primary_10_3389_fendo_2024_1400961 crossref_primary_10_1002_cph4_70053 crossref_primary_10_1016_j_peptides_2025_171381 crossref_primary_10_1016_j_jacl_2025_09_002 crossref_primary_10_1007_s12035_025_04989_0 |
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| Keywords | Type 2 diabetes Ceramide Cardiovascular disease Liraglutide |
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| PublicationTitle | Lipids in health and disease |
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Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the... Background Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the... Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the glucagon-like... BackgroundSpecific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the... Abstract Background Specific ceramides have been identified as risk markers for cardiovascular disease (CVD) years before onset of disease. Treatment with the... |
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| SubjectTerms | 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 |
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| Title | Ceramides are decreased after liraglutide treatment in people with type 2 diabetes: a post hoc analysis of two randomized clinical trials |
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