Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.

Autor: Anholm C; Department of Internal Medicine, Copenhagen University Hospital, Glostrup, Denmark; Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark. Electronic address: canholm@youmail.dk., Kumarathurai P; Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark., Pedersen LR; Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark., Samkani A; Department of Endocrinology, Copenhagen University Hospital, Bispebjerg, Denmark., Walzem RL; Department of Poultry Science and Faculty of Nutrition, Texas A&M University, Texas, USA., Nielsen OW; Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark., Kristiansen OP; Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark., Fenger M; Department of Clinical Biochemistry, Copenhagen University Hospital, Hvidovre, Denmark., Madsbad S; Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark., Sajadieh A; Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark., Haugaard SB; Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark; Department of Endocrinology, Copenhagen University Hospital, Bispebjerg, Denmark.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2019 Sep; Vol. 288, pp. 60-66. Date of Electronic Publication: 2019 Jul 05.
DOI: 10.1016/j.atherosclerosis.2019.07.007
Abstrakt: Background and Aims: Atherosclerosis in obesity and type 2 diabetes (T2DM) is associated with low-grade inflammation (LGI) and dyslipidemia, where especially small, dense lipoprotein particles are atherogenic. The glucagon-like peptide-1 receptor agonist, liraglutide, reduces cardiovascular events by poorly understood mechanisms. We investigated the effect of liraglutide combined with metformin on LGI and lipoprotein density profiles in patients with stable coronary artery disease (CAD) and newly diagnosed T2DM.
Methods: We conducted a randomized, double-blind, placebo-controlled, cross-over trial over a 12 + 12-week period, with ≥2-week wash-out.
Intervention: liraglutide/metformin vs. placebo/metformin. Lipoproteins were separated by continuous density gradient ultracentrifugation, and LDL divided into five subfractions between 226 and 270 Å, considering particle size ≤255 Å as the atherogenic pattern. Plasma C-reactive protein and tumor necrosis factor-α were assessed by the enzyme-linked immunosorbent-assay.
Results: 28 out of 41 randomized patients completed all visits. Intention-to-treat analysis was performed but one patient had statin dosage and was excluded from the analysis. 95% of the patients were on statin therapy. Overall, liraglutide did not affect lipid subfractions or markers of LGI compared to placebo. The combination of liraglutide and metformin reduced the total LDL subfractions, primarily by reducing the most atherogenic subfraction LDL 5 , and reduced CRP but not TNF-α. Explorative analyses suggested that the subfraction LDL 5 during the wash-out period rebounded significantly at least in a per-protocol analysis of the sub-group of patients starting the liraglutide therapy.
Conclusions: In patients with CAD and newly diagnosed T2DM on stable statin therapy, liraglutide combined with metformin may improve the atherogenic LDL lipid profile and CRP.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: