TY - JOUR

T1 - Liraglutide Lowers Palmitoleate Levels in Type 2 Diabetes

T2 - A Post Hoc Analysis of the LIRAFLAME Randomized Placebo-Controlled Trial

AU - Wretlind, Asger

AU - Zobel, Emilie Hein

AU - De Zawadzki, Andressa

AU - Ripa, Rasmus Sejersten

AU - Curovic, Viktor Rotbain

AU - Von Scholten, Bernt Johan

AU - Mattila, Ismo Matias

AU - Hansen, Tine Willum

AU - Kjær, Andreas

AU - Vestergaard, Henrik

AU - Rossing, Peter

AU - Legido-Quigley, Cristina

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.3389/fcdhc.2022.856485

DO - 10.3389/fcdhc.2022.856485

M3 - Journal article

C2 - 36992761

VL - 3

JO - Frontiers in Clinical Diabetes and Healthcare

JF - Frontiers in Clinical Diabetes and Healthcare

SN - 2673-6616

M1 - 856485

ER -