Ceramides and phospholipids are downregulated with liraglutide treatment: results from the LiraFlame randomized controlled trial
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Ceramides and phospholipids are downregulated with liraglutide treatment : results from the LiraFlame randomized controlled trial. / Zobel, Emilie H; Wretlind, Asger; Ripa, Rasmus S; Rotbain Curovic, Viktor; von Scholten, Bernt J; Suvitaival, Tommi; Hansen, Tine W; Kjær, Andreas; Legido-Quigley, Cristina; Rossing, Peter.
I: BMJ open diabetes research & care, Bind 9, Nr. 1, e002395, 09.2021, s. 1-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Ceramides and phospholipids are downregulated with liraglutide treatment
T2 - results from the LiraFlame randomized controlled trial
AU - Zobel, Emilie H
AU - Wretlind, Asger
AU - Ripa, Rasmus S
AU - Rotbain Curovic, Viktor
AU - von Scholten, Bernt J
AU - Suvitaival, Tommi
AU - Hansen, Tine W
AU - Kjær, Andreas
AU - Legido-Quigley, Cristina
AU - Rossing, Peter
PY - 2021/9
Y1 - 2021/9
N2 - INTRODUCTION: Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can reduce risk of cardiovascular disease (CVD) in persons living with type 2 diabetes, however the mechanisms explaining this cardiovascular benefit are still debated. We investigated changes in the plasma lipidome following treatment with the GLP-1 RA liraglutide.RESEARCH DESIGN AND METHODS: In a double-blind placebo-controlled trial, we randomized 102 persons with type 2 diabetes to liraglutide or placebo for 26 weeks. Fasting blood plasma was collected at baseline and at end-of-treatment. The lipidome was measured using liquid-chromatography-coupled mass-spectrometry as a secondary end point in the study. Treatment response of each lipid was tested with lipid-specific linear mixed-effect models comparing liraglutide with placebo. Bonferroni p<7.1e-03 was employed. The independence of the findings from clinical covariates was evaluated with adjustment for body mass index, HbA1c, fasting status, lipid-lowering treatment and change in lipid-lowering treatment during the trial.RESULTS: In total, 260 lipids were identified covering 11 lipid families. We observed significant decreases following liraglutide treatment compared with placebo in 21 lipids (p<7.1e-03) from the following lipid families: ceramides, hexocyl-ceramides, phosphatidylcholines, phosphatidylethanolamines and triglycerides. We confirmed these findings in adjusted models (p≤0.01). In the liraglutide-treated group, the individual lipids were reduced in the range of 14%-61% from baseline level, compared with 19% decrease to 27% increase from baseline level in the placebo group.CONCLUSIONS: Compared with placebo, liraglutide treatment led to a significant downregulation in ceramides, phospholipids and triglycerides, which all are linked to higher risk of CVD. These findings were independent of relevant clinical covariates. Our findings are hypothesis generating and shed light on the biological mechanisms underlying the cardiovascular benefits observed with GLP-1 RAs in outcome studies, and further strengthen the evidence base for recommending GLP-1 RAs to prevent CVD in type 2 diabetes.TRIAL REGISTRATION NUMBER: NCT03449654.
AB - INTRODUCTION: Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can reduce risk of cardiovascular disease (CVD) in persons living with type 2 diabetes, however the mechanisms explaining this cardiovascular benefit are still debated. We investigated changes in the plasma lipidome following treatment with the GLP-1 RA liraglutide.RESEARCH DESIGN AND METHODS: In a double-blind placebo-controlled trial, we randomized 102 persons with type 2 diabetes to liraglutide or placebo for 26 weeks. Fasting blood plasma was collected at baseline and at end-of-treatment. The lipidome was measured using liquid-chromatography-coupled mass-spectrometry as a secondary end point in the study. Treatment response of each lipid was tested with lipid-specific linear mixed-effect models comparing liraglutide with placebo. Bonferroni p<7.1e-03 was employed. The independence of the findings from clinical covariates was evaluated with adjustment for body mass index, HbA1c, fasting status, lipid-lowering treatment and change in lipid-lowering treatment during the trial.RESULTS: In total, 260 lipids were identified covering 11 lipid families. We observed significant decreases following liraglutide treatment compared with placebo in 21 lipids (p<7.1e-03) from the following lipid families: ceramides, hexocyl-ceramides, phosphatidylcholines, phosphatidylethanolamines and triglycerides. We confirmed these findings in adjusted models (p≤0.01). In the liraglutide-treated group, the individual lipids were reduced in the range of 14%-61% from baseline level, compared with 19% decrease to 27% increase from baseline level in the placebo group.CONCLUSIONS: Compared with placebo, liraglutide treatment led to a significant downregulation in ceramides, phospholipids and triglycerides, which all are linked to higher risk of CVD. These findings were independent of relevant clinical covariates. Our findings are hypothesis generating and shed light on the biological mechanisms underlying the cardiovascular benefits observed with GLP-1 RAs in outcome studies, and further strengthen the evidence base for recommending GLP-1 RAs to prevent CVD in type 2 diabetes.TRIAL REGISTRATION NUMBER: NCT03449654.
KW - Ceramides
KW - Diabetes Mellitus, Type 2/drug therapy
KW - Glucagon-Like Peptide 1
KW - Humans
KW - Liraglutide/therapeutic use
KW - Phospholipids
U2 - 10.1136/bmjdrc-2021-002395
DO - 10.1136/bmjdrc-2021-002395
M3 - Journal article
C2 - 34518158
VL - 9
SP - 1
EP - 9
JO - B M J Open Diabetes Research & Care
JF - B M J Open Diabetes Research & Care
SN - 2052-4897
IS - 1
M1 - e002395
ER -
ID: 283513406