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Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial
BACKGROUND: Liraglutide is a glucose-lowering medication used to treat type 2 diabetes and obesity. It is a GLP-1 receptor agonist with downstream metabolic changes beyond the incretin system, such as reducing the risk of cardiovascular complications. The understanding of these changes is critical f...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012104/ https://www.ncbi.nlm.nih.gov/pubmed/36992761 http://dx.doi.org/10.3389/fcdhc.2022.856485 |
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author | Wretlind, Asger Zobel, Emilie Hein de Zawadzki, Andressa Ripa, Rasmus Sejersten Curovic, Viktor Rotbain von Scholten, Bernt Johan Mattila, Ismo Matias Hansen, Tine Willum Kjær, Andreas Vestergaard, Henrik Rossing, Peter Legido-Quigley, Cristina |
author_facet | Wretlind, Asger Zobel, Emilie Hein de Zawadzki, Andressa Ripa, Rasmus Sejersten Curovic, Viktor Rotbain von Scholten, Bernt Johan Mattila, Ismo Matias Hansen, Tine Willum Kjær, Andreas Vestergaard, Henrik Rossing, Peter Legido-Quigley, Cristina |
author_sort | Wretlind, Asger |
collection | PubMed |
description | BACKGROUND: Liraglutide is a glucose-lowering medication used to treat type 2 diabetes and obesity. It is a GLP-1 receptor agonist with downstream metabolic changes beyond the incretin system, such as reducing the risk of cardiovascular complications. The understanding of these changes is critical for improving treatment outcomes. Herein, we present a post hoc experimental analysis using metabolomic phenotyping to discover molecular mecphanisms in response to liraglutide. METHOD: Plasma samples were obtained from The LiraFlame Study (ClinicalTrials.gov identifier: NCT03449654), a randomized double-blinded placebo-controlled clinical trial, including 102 participants with type 2 diabetes randomized to either liraglutide or placebo treatment for 26 weeks. Mass spectrometry-based metabolomics analyses were carried out on samples from baseline and the end of the trial. Metabolites (n=114) were categorized into pathways and linear mixed models were constructed to evaluate the association between changes in metabolites and liraglutide treatment. RESULTS: We found the free fatty acid palmitoleate was significantly reduced in the liraglutide group compared to placebo (adjusted for multiple testing p-value = 0.04). The activity of stearoyl-CoA desaturase-1 (SCD1), the rate limiting enzyme for converting palmitate into palmitoleate, was found significantly downregulated by liraglutide treatment compared to placebo (p-value = 0.01). These metabolic changes have demonstrated to be linked to insulin sensitivity and cardiovascular health. |
format | Online Article Text |
id | pubmed-10012104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100121042023-03-28 Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial Wretlind, Asger Zobel, Emilie Hein de Zawadzki, Andressa Ripa, Rasmus Sejersten Curovic, Viktor Rotbain von Scholten, Bernt Johan Mattila, Ismo Matias Hansen, Tine Willum Kjær, Andreas Vestergaard, Henrik Rossing, Peter Legido-Quigley, Cristina Front Clin Diabetes Healthc Clinical Diabetes and Healthcare BACKGROUND: Liraglutide is a glucose-lowering medication used to treat type 2 diabetes and obesity. It is a GLP-1 receptor agonist with downstream metabolic changes beyond the incretin system, such as reducing the risk of cardiovascular complications. The understanding of these changes is critical for improving treatment outcomes. Herein, we present a post hoc experimental analysis using metabolomic phenotyping to discover molecular mecphanisms in response to liraglutide. METHOD: Plasma samples were obtained from The LiraFlame Study (ClinicalTrials.gov identifier: NCT03449654), a randomized double-blinded placebo-controlled clinical trial, including 102 participants with type 2 diabetes randomized to either liraglutide or placebo treatment for 26 weeks. Mass spectrometry-based metabolomics analyses were carried out on samples from baseline and the end of the trial. Metabolites (n=114) were categorized into pathways and linear mixed models were constructed to evaluate the association between changes in metabolites and liraglutide treatment. RESULTS: We found the free fatty acid palmitoleate was significantly reduced in the liraglutide group compared to placebo (adjusted for multiple testing p-value = 0.04). The activity of stearoyl-CoA desaturase-1 (SCD1), the rate limiting enzyme for converting palmitate into palmitoleate, was found significantly downregulated by liraglutide treatment compared to placebo (p-value = 0.01). These metabolic changes have demonstrated to be linked to insulin sensitivity and cardiovascular health. Frontiers Media S.A. 2022-03-04 /pmc/articles/PMC10012104/ /pubmed/36992761 http://dx.doi.org/10.3389/fcdhc.2022.856485 Text en Copyright © 2022 Wretlind, Zobel, de Zawadzki, Ripa, Curovic, von Scholten, Mattila, Hansen, Kjær, Vestergaard, Rossing and Legido-Quigley https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Clinical Diabetes and Healthcare Wretlind, Asger Zobel, Emilie Hein de Zawadzki, Andressa Ripa, Rasmus Sejersten Curovic, Viktor Rotbain von Scholten, Bernt Johan Mattila, Ismo Matias Hansen, Tine Willum Kjær, Andreas Vestergaard, Henrik Rossing, Peter Legido-Quigley, Cristina Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial |
title | Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial |
title_full | Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial |
title_fullStr | Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial |
title_full_unstemmed | Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial |
title_short | Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial |
title_sort | liraglutide lowers palmitoleate levels in type 2 diabetes. a post hoc analysis of the liraflame randomized placebo-controlled trial |
topic | Clinical Diabetes and Healthcare |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10012104/ https://www.ncbi.nlm.nih.gov/pubmed/36992761 http://dx.doi.org/10.3389/fcdhc.2022.856485 |
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