OBJECTIVE Long-term treatment with up to 1.8 mg liraglutide improves cardiovascular and all-cause mortality in patients with type 2 diabetes at high risk for cardiovascular disease (CVD) and is currently under investigation in subjects without diabetes. Aim of our study was to investigate whether high dose (3 mg) short-term (5 weeks) treatment with liraglutide in obese patients with no overt type 2 diabetes affects metabolites, lipid and lipoprotein profile and components of activin-follistatin axis in cardiovascular beneficial or detrimental way. RESEARCH DESIGN AND METHODS Twenty obese patients participated in a randomized, placebo-controlled, cross-over, double-blind study and were administrated liraglutide 3 mg or placebo for 5 weeks. Metabolites, fatty acids, lipid-lipoprotein profile and concentrations of activins and follistatins (250 parameters) were assessed in serum at start and completion of each treatment. RESULTS Concentrations of important cardiovascular markers such as total, free and remnant cholesterol were reduced with liraglutide before and after adjusting for weight loss. Similarly, reductions in number of small and medium size LDL particles and in their total lipid concentration were observed with liraglutide and partially weight-loss related. Tyrosine levels were reduced and behenic acid levels were increased whereas only minor changes were observed in HDL, VLDL and IDL. Concentrations of activin AB and follistatin were significantly reduced in liraglutide-treated group. CONCLUSIONS Treatment of obese patients without overt type 2 diabetes with high dose of liraglutide for a short period of time induces changes in lipid-lipoprotein and hormonal profile that are suggestive of lower risk of atherosclerosis and CVD. Trial registration ClinicalTrials.gov Identifier: NCT02944500. Study ID Number 2015P000327. Registered November 2016.

中文翻译：

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在没有明显的2型糖尿病的肥胖患者中，高剂量利拉鲁肽的短期治疗可改善脂质和脂蛋白谱并改变脂质代谢的激素介体：一项随机，安慰剂对照，交叉，双盲的临床试验。

目的长期使用高达1.8毫克的利拉鲁肽治疗可改善患有高心血管疾病（CVD）风险的2型糖尿病患者的心血管和全因死亡率，目前正在对无糖尿病的受试者进行研究。我们的研究目的是调查在没有明显2型糖尿病的肥胖患者中使用高剂量（3 mg）短期（5周）利拉鲁肽治疗是否对心血管有益于代谢物，脂质和脂蛋白谱以及激活素-卵泡抑素轴成分或有害的方式。研究设计与方法20名肥胖患者参加了一项随机，安慰剂对照，交叉，双盲研究，并给予5周利拉鲁肽或安慰剂3周。代谢物，脂肪酸，在每次治疗开始和结束时评估血清中的脂质-脂蛋白谱以及激活素和卵泡抑素的浓度（250个参数）。结果在调整体重减轻前后，利拉鲁肽降低了重要的心血管标志物的浓度，例如总胆固醇，游离胆固醇和残留胆固醇。同样，与利拉鲁肽和部分体重减轻有关，观察到中小尺寸LDL颗粒数量减少，总脂质浓度降低。酪氨酸水平降低，山hen酸水平升高，而在HDL，VLDL和IDL中仅观察到微小变化。利拉鲁肽治疗组中激活素AB和卵泡抑素的浓度显着降低。结论在短时间内用高剂量的利拉鲁肽治疗无明显2型糖尿病的肥胖患者，可引起脂质-脂蛋白和激素水平的改变，提示动脉粥样硬化和CVD的风险较低。试用注册ClinicalTrials.gov标识符：NCT02944500。研究编号2015P000327。2016年11月注册。