Department of Promoting Health, Maternal-Infant, Excellence and Internal and Specialized Medicine (ProMISE) G. D'Alessandro, University of Palermo (Italy), Piazza delle Cliniche n.2, 90127, Palermo, Italy.
Internal Medicine and Stroke Care Ward, Policlinico 'P. Giaccone', Palermo, Italy.
Cardiovasc Diabetol. 2021 Jan 4;20(1):1. doi: 10.1186/s12933-020-01183-5.
Recent cardiovascular outcome trials have shown significant reductions in major cardiovascular (CV) events with glucagon-like peptide (GLP)-1 receptor agonists. Additionally, adjunctive surrogates for cardiovascular risk validated by some studies include arterial stiffness and endothelial function indexes. To date, no randomized trial has addressed the possible effects of antidiabetic interventional drugs such as GLP1 agonists on endothelial and arterial stiffness indexes as surrogate markers of vascular damage.
We aimed to evaluate metabolic efficacy and surrogate vascular efficacy endpoints of once-weekly dulaglutide (1.5 mg) plus traditional antidiabetic treatment compared with traditional antidiabetic treatment alone in subjects with type 2 diabetes.
Men and women (aged ≥ 50 years) with established or newly detected type 2 diabetes whose HbA1c level was 9.5% or less on stable doses of up to two oral glucose- lowering drugs with or without basal insulin therapy were eligible for randomization. Subcutaneous dulaglutide was initiated at the full dose (1.5 mg/day weekly). Arterial stiffness (PWV: pulse wave velocity and augmentation index) and endothelial function (RHI: reactive hyperaemia index) were evaluated at baseline and at three-month and nine-month examination visits. At each visit (at 3 and 9 months), the subjects were also evaluated for glycaemic variables such as fasting plasma glucose (FPG) and HbA1c and lipid variables such as total cholesterol, LDL cholesterol, HDL cholesterol and triglyceride levels.
At the three-month follow-up, the subjects treated with dulaglutide showed significantly lower serum levels of FPG and HbA1c than control subjects treated with conventional therapy. At the 9-month follow-up, subjects treated with dulaglutide showed significant lower values of the mean diastolic blood pressure, BMI, total serum cholesterol, LDL cholesterol, FPG, HbA1c and PWV and higher mean RHI values than control subjects treated with conventional therapy.
Our randomized trial showed that subjects with type 2 diabetes treated with conventional therapy plus 1.5 mg/day of subcutaneous dulaglutide compared with subjects treated with conventional therapy alone showed favourable metabolic effects associated with positive effects on vascular health markers such as arterial stiffness and endothelial function markers. These findings are consistent with previous study findings indicating the strict relationship between cardiovascular risk factors such as systolic blood pressure, total serum cholesterol and LDL levels and cardiovascular events and vascular health surrogate markers.
最近的心血管结局试验表明，胰高血糖素样肽（GLP）-1 受体激动剂可显著降低主要心血管（CV）事件。此外，一些研究验证的心血管风险的辅助替代指标包括动脉僵硬和内皮功能指数。迄今为止，尚无随机试验研究抗糖尿病干预药物（如 GLP1 激动剂）对作为血管损伤替代标志物的内皮和动脉僵硬指数的可能影响。
我们旨在评估每周一次的度拉鲁肽（1.5mg）联合传统降糖治疗与单独传统降糖治疗在 2 型糖尿病患者中的代谢疗效和替代血管疗效终点。
年龄≥50 岁的男性和女性（已确诊或新诊断为 2 型糖尿病），其在接受最大剂量至两种口服降糖药物联合或不联合基础胰岛素治疗时的糖化血红蛋白（HbA1c）水平＜9.5%，有资格进行随机分组。皮下给予度拉鲁肽起始剂量为 1.5mg/天，每周一次。基线时及 3 个月和 9 个月检查时评估动脉僵硬（PWV：脉搏波速度和增强指数）和内皮功能（RHI：反应性充血指数）。每次就诊（在 3 个月和 9 个月时）还评估空腹血糖（FPG）和 HbA1c 等血糖变量以及总胆固醇、LDL 胆固醇、HDL 胆固醇和甘油三酯水平等血脂变量。
在 3 个月的随访中，接受度拉鲁肽治疗的患者的血清 FPG 和 HbA1c 水平明显低于接受常规治疗的对照组。在 9 个月的随访中，接受度拉鲁肽治疗的患者的平均舒张压、BMI、总血清胆固醇、LDL 胆固醇、FPG、HbA1c 和 PWV 值显著降低，而常规治疗对照组的 RHI 值显著升高。
我们的随机试验表明，与单独接受常规治疗的患者相比，接受常规治疗联合 1.5mg/天皮下度拉鲁肽治疗的 2 型糖尿病患者表现出有利的代谢效应，同时对动脉僵硬和内皮功能等血管健康标志物也具有积极影响。这些发现与之前的研究结果一致，表明心血管风险因素（如收缩压、总血清胆固醇和 LDL 水平）与心血管事件和血管健康替代标志物之间存在密切关系。
