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

Wretlind, Asger and Zobel, Emilie Hein and de Zawadzki, Andressa and Ripa, Rasmus Sejersten and Curovic, Viktor Rotbain and von Scholten, Bernt Johan and Mattila, Ismo Matias and Hansen, Tine Willum and Kjær, Andreas and Vestergaard, Henrik and Rossing, Peter and Legido-Quigley, Cristina (2022) Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes. A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial. Frontiers in Clinical Diabetes and Healthcare, 3. ISSN 2673-6616

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Abstract

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.

Item Type: Article
Subjects: Journal Eprints > Medical Science
Depositing User: Managing Editor
Date Deposited: 02 Jan 2023 11:51
Last Modified: 16 Apr 2024 04:19
URI: http://repository.journal4submission.com/id/eprint/274

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