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

Dragana Nikolic, Rosaria Vincenza Giglio, Ali A Rizvi, Angelo Maria Patti, Giuseppe Montalto, Francesco Maranta, Domenico Cianflone, Anca Pantea Stoian, Manfredi Rizzo, Dragana Nikolic, Rosaria Vincenza Giglio, Ali A Rizvi, Angelo Maria Patti, Giuseppe Montalto, Francesco Maranta, Domenico Cianflone, Anca Pantea Stoian, Manfredi Rizzo

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.

Keywords: Cardiovascular risk; Carotid intima-media thickness; Lipoproteins; Liraglutide; Small dense low-density lipoproteins; Type 2 diabetes.

Figures

Fig. 1
Fig. 1
Lipoprotein profile of a representative subject at baseline (a) and after 4 months of liraglutide therapy (b). LDL Low-density lipoprotein, cIMT carotid intima-media thickness
Fig. 2
Fig. 2
Correlation plot of changes in cIMT and changes in small dense LDL-3 subclass after liraglutide therapy

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Source: PubMed

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