Liraglutide Reduces Carotid Intima-Media Thickness by Reducing Small Dense Low-Density Lipoproteins in a Real-World Setting of Patients with Type 2 Diabetes: A Novel Anti-Atherogenic Effect

• Type of Material: Article
• Authors: Dragana Nikolic, University of Palermo; Rosaria Vincenza Giglio, University of Palermo; Ali A. Rizvi, Emory University; Angelo Maria Patti, University of Palermo; Giuseppe Montalto, University of Palermo; Francesco Maranta, San Raffaele Vita-Salute University, Italy; Domenico Cianflone, San Raffaele Vita-Salute University, Italy; Anca Pantea Stoian, Carol Davila University of Medicine & Pharmacy; Manfredi Rizzo, University of Palermo
• Language: English
• Date: 2020-11-18
• Publisher: Springer Heidelberg
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1007/s13300-020-00962-3
• Title of Journal or Parent Work: Diabetes Therapy
• Volume: 12
• Issue: 1
• Start Page: 261
• End Page: 274
• Grant/Funding Information: Part of this work was carried out using instruments provided by the Euro-Mediterranean Institute of Science and Technology and funded with the Italian National Operational Programme for Research and Competitiveness 2007–2013 grant awarded to the project titled "CyberBrain-Polo di innovazione" (Project code: PONa3_00210, European Regional Development Fund).; No Rapid Service Fee was received by the journal for the publication of this article.; This original article was written independently of any pharmaceutical company, including Novo Nordisk. The authors did not receive any financial or professional help with the preparation of the manuscript. No industry relation has had any impact on the manuscript.
• Keywords: Science & Technology; Life Sciences & Biomedicine; Metformin; Carotid intima-media thickness; Cardiovascular risk factors; Mellitus; Responses; Pioglitazone; Liraglutide; Cardiovascular risk; Lipoproteins; Modulation; Clinical relevance; LDL size; Type 2 diabetes; Endocrinology & Metabolism; Therapies; Small dense low-density lipoproteins; Subclasses
• Research Categories: Health Sciences, Health Care Management; Health Sciences, Public Health; Health Sciences, Nutrition; Health Sciences, Medicine and Surgery

Abstract

Introduction: Liraglutide has several non-glycemic effects, including those on plasma lipids and lipoproteins, contributing to its cardiovascular benefit; however, the exact underlying mechanisms remain unclear. We investigated a novel anti-atherogenic effect of liraglutide in a real-world prospective study on patients with type 2 diabetes (T2DM). Methods: Sixty-two patients with T2DM (31 men, 31 women; mean age ± standard deviation 61 ± 9 years) naïve to incretin-based therapies were treated with liraglutide (1.2 mg/day) as add-on therapy to metformin (1500–3000 mg/day) for 4 months. Laboratory analyses included the assessment of lipoprotein subclass profile by gel electrophoresis (Lipoprint; Quantimetrix Corp., Redondo Beach, CA, USA). Carotid intima-media thickness (cIMT) was assessed by Doppler ultrasonography. Statistical analyses included the paired t test, Spearman correlation and multiple regression analysis. Results: The addition of liraglutide to metformin monotherapy resulted in significant reductions in fasting glycemia, hemoglobin A1c, body mass index, waist circumference, total cholesterol, triglycerides and low-density lipoprotein (LDL)-cholesterol, as well as in cIMT. There was an increase in the large LDL-1 subfraction, with a concomitant reduction in atherogenic small dense LDL-3 and LDL-4 subfractions. Correlation analysis revealed a significant association between changes in cIMT and changes in small dense LDL-3 subfraction (r = 0.501; p < 0.0001). Multivariate analysis, including all of the measured anthropometric and laboratory parameters, revealed that only changes in the small dense LDL-3 subfraction were independent predictors of changes in cIMT (p < 0.0001). Conclusion: Our findings are the first to show that the vascular benefit of liraglutide in patients with T2DM is associated with reductions in atherogenic small dense LDL. This effect is independent of glycemic control and body weight reduction and may represent one of the key mechanisms by which liraglutide is able to reduce cardiovascular events. Trial Registration: ClinicalTrials.gov: NCT01715428.