Nikolic Dragana, Giglio Rosaria Vincenza, Rizvi Ali A, Patti Angelo Maria, Montalto Giuseppe, Maranta Francesco, Cianflone Domenico, Stoian Anca Pantea, Rizzo Manfredi
Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.
Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
Diabetes Ther. 2021 Jan;12(1):261-274. doi: 10.1007/s13300-020-00962-3. Epub 2020 Nov 18.
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).
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.
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).
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.
ClinicalTrials.gov: NCT01715428.
利拉鲁肽具有多种非血糖效应，包括对血浆脂质和脂蛋白的作用，这有助于其心血管获益；然而，确切的潜在机制仍不清楚。我们在一项针对2型糖尿病（T2DM）患者的真实世界前瞻性研究中，研究了利拉鲁肽一种新的抗动脉粥样硬化作用。
62例初治的T2DM患者（31例男性，31例女性；平均年龄±标准差61±9岁），在二甲双胍（1500 - 3000mg/天）基础上加用利拉鲁肽（1.2mg/天）作为附加治疗，持续4个月。实验室分析包括通过凝胶电泳（Lipoprint；美国加利福尼亚州雷东多海滩的Quantimetrix公司）评估脂蛋白亚类谱。通过多普勒超声评估颈动脉内膜中层厚度（cIMT）。统计分析包括配对t检验、Spearman相关性分析和多元回归分析。
在二甲双胍单药治疗基础上加用利拉鲁肽，可显著降低空腹血糖、糖化血红蛋白、体重指数、腰围、总胆固醇、甘油三酯和低密度脂蛋白（LDL）胆固醇，以及cIMT。大LDL - 1亚组分增加，同时致动脉粥样硬化的小而密LDL - 3和LDL - 4亚组分减少。相关性分析显示，cIMT变化与小而密LDL - 3亚组分变化之间存在显著关联（r = 0.501；p < 0.0001）。包括所有测量的人体测量学和实验室参数的多变量分析显示，只有小而密LDL - 3亚组分的变化是cIMT变化的独立预测因素（p < 0.0001）。
我们的研究结果首次表明，利拉鲁肽对T2DM患者的血管益处与致动脉粥样硬化的小而密LDL减少有关。这种作用独立于血糖控制和体重减轻，可能代表利拉鲁肽能够减少心血管事件的关键机制之一。
ClinicalTrials.gov：NCT01715428。
