Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial

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...

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Veröffentlicht in:Frontiers in clinical diabetes and healthcare (online) Jg. 3; S. 856485
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland Frontiers Media S.A 04.03.2022
Schlagworte:
Clinical Diabetes and Healthcare
GLP-1 RA
liraglutide
palmitoleate
palmitoleic acid
stearoyl-CoA 9-desaturase 1 (SCD1)
type 2 diabetes (T2D)
liraglutide
GLP-1 RA
palmitoleic acid
stearoyl-CoA 9-desaturase 1 (SCD1)
type 2 diabetes (T2D)
monounsaturated fatty acid (MUFA)
palmitoleate
ISSN:2673-6616, 2673-6616
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Zusammenfassung: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 experimental analysis using metabolomic phenotyping to discover molecular mecphanisms in response to liraglutide. 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. 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.
Bibliographie:ObjectType-Article-1
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Edited by: Mustafa Cesur, Güven Hospital, Turkey
Reviewed by: Emre Bozkirli, Acıbadem Adana Hospital, Turkey; Irmak Sayın Alan, Güven Hospital, Turkey
This article was submitted to Diabetes Cardiovascular Complications, a section of the journal Frontiers in Clinical Diabetes and Healthcare
These authors have contributed equally to this work and share last authorship
ISSN:2673-6616
2673-6616
DOI:10.3389/fcdhc.2022.856485