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

Autor:	Wretlind A; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Zobel EH; Steno Diabetes Center Copenhagen, Herlev, Denmark., de Zawadzki A; Steno Diabetes Center Copenhagen, Herlev, Denmark., Ripa RS; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Curovic VR; Steno Diabetes Center Copenhagen, Herlev, Denmark., von Scholten BJ; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Novo Nordisk AS, Bagsvaerd, Denmark., Mattila IM; Steno Diabetes Center Copenhagen, Herlev, Denmark., Hansen TW; Steno Diabetes Center Copenhagen, Herlev, Denmark., Kjær A; Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark., Vestergaard H; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Bornholms Hospital, Rønne, Denmark., Rossing P; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Legido-Quigley C; Steno Diabetes Center Copenhagen, Herlev, Denmark.; Institute of Pharmaceutical Science, King's College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	Frontiers in clinical diabetes and healthcare [Front Clin Diabetes Healthc] 2022 Mar 04; Vol. 3, pp. 856485. Date of Electronic Publication: 2022 Mar 04 (Print Publication: 2022).
DOI:	10.3389/fcdhc.2022.856485
Abstrakt:	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. Competing Interests: EZ and BS are now employees of Novo Nordisk A/S, work related to this article was done when EZ was employed by Steno Diabetes Center Copenhagen. TH, RR, and PR have shares in Novo Nordisk A/S. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Wretlind, Zobel, de Zawadzki, Ripa, Curovic, von Scholten, Mattila, Hansen, Kjær, Vestergaard, Rossing and Legido-Quigley.)
Databáze:	MEDLINE
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