Institute for Clinical Research and Development, Medical Department, Mainz, Germany.
Diabet Med. 2012 Sep;29(9):1115-8. doi: 10.1111/j.1464-5491.2012.03589.x.
The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy.
Forty-four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA(1c) < 53 mmol/mol (7.0%), age 30-65 years. Patients were randomized to receive additional liraglutide or to remain on metformin monotherapy. After 6 weeks (1.2 mg) and after 12 weeks (1.8 mg), venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function. In addition, retinal microvascular endothelial function and arterial stiffness were measured.
HbA(1c) levels declined from 45 ± 4 mmol/mol (6.3 ± 0.4%; mean ± SD) to 40 ± 3 mmol/mol (5.8 ± 0.3%) during liraglutide treatment. Asymmetric dimethylarginin was reduced by liraglutide treatment from 0.39 ± 0.08 to 0.35 ± 0.06 μmol/l, E-selectin from 43.6 ± 15.4 to 40.8 ± 15.1 ng/ml, plasminogen activator inhibitor 1 from 861.6 ± 584.3 to 666.1 ± 499.4 ng/ml and intact proinsulin from 9.0 ± 7.2 to 7.0 ± 4.8 pmol/l at 12 weeks of treatment. The microvascular response to flicker light increased from 7.0 ± 15.1 to 15.4 ± 11.5% after 6 weeks and to 11.1 ± 9.9% after 12 weeks. No change could be observed for high-sensitivity C-reactive protein, monocyte chemotactic protein 1, vascular cell adhesion molecule or arterial stiffness parameters.
In patients with Type 2 diabetes, well controlled with metformin monotherapy, addition of liraglutide improves several cardiovascular risk markers beyond glycaemic control.
本研究旨在探讨利拉鲁肽对二甲双胍单药控制良好的 2 型糖尿病患者的血管作用。
本研究纳入 44 例 2 型糖尿病患者。主要纳入标准为:服用稳定剂量二甲双胍治疗,糖化血红蛋白(HbA1c)<53mmol/mol(7.0%),年龄 30-65 岁。患者随机分为接受利拉鲁肽加用组或继续接受二甲双胍单药治疗组。治疗 6 周(1.2mg)和 12 周(1.8mg)后,采集静脉血测量血管和内皮功能的多个实验室标志物。此外,还测量视网膜微血管内皮功能和动脉僵硬度。
利拉鲁肽治疗后,HbA1c 水平从 45±4mmol/mol(6.3±0.4%;平均值±标准差)降至 40±3mmol/mol(5.8±0.3%)。利拉鲁肽治疗使不对称二甲基精氨酸从 0.39±0.08μmol/L 降至 0.35±0.06μmol/L,E-选择素从 43.6±15.4ng/ml 降至 40.8±15.1ng/ml,纤溶酶原激活物抑制剂 1 从 861.6±584.3ng/ml 降至 666.1±499.4ng/ml,完整胰岛素原从 9.0±7.2pmol/L 降至 7.0±4.8pmol/L,12 周时,闪烁光微血流反应从 7.0±15.1%增加至 15.4±11.5%,6 周后增加至 11.1±9.9%。高敏 C 反应蛋白、单核细胞趋化蛋白 1、血管细胞黏附分子或动脉僵硬度参数无变化。
在二甲双胍单药控制良好的 2 型糖尿病患者中,加用利拉鲁肽可改善血糖控制以外的多种心血管风险标志物。