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

Autor: Asger Wretlind, Emilie Hein Zobel, Andressa de Zawadzki, Rasmus Sejersten Ripa, Viktor Rotbain Curovic, Bernt Johan von Scholten, Ismo Matias Mattila, Tine Willum Hansen, Andreas Kjær, Henrik Vestergaard, Peter Rossing, Cristina Legido-Quigley
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Frontiers in Clinical Diabetes and Healthcare, Vol 3 (2022)
Druh dokumentu: article
ISSN: 2673-6616
DOI: 10.3389/fcdhc.2022.856485
Popis: BackgroundLiraglutide 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.MethodPlasma 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.ResultsWe 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.
Databáze: Directory of Open Access Journals