Sun Feng, Wu Shanshan, Wang Jing, Guo Shuxia, Chai Sanbao, Yang Zhirong, Li Lishi, Zhang Yuan, Ji Linong, Zhan Siyan
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China; Department of Preventive Medicine, College of Medicine, Shihezi University, Shihezi, China.
Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
Clin Ther. 2015 Jan 1;37(1):225-241.e8. doi: 10.1016/j.clinthera.2014.11.008. Epub 2014 Dec 29.
The goal of this study was to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on lipid profiles in patients with type 2 diabetes.
The MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched from inception through October 31, 2013. Randomized controlled trials with available data were selected if they compared GLP-1 RAs with placebo and traditional antidiabetic drugs with a duration ≥8 weeks. The weighted mean difference for changes in lipid profiles was estimated by using the random effects model, and a network meta-analysis was performed to supplement direct comparisons.
Thirty-five trials with 13 treatments were included in the analysis. GLP-1 RAs decreased HDL-C with a range of -0.06 mmol/L (95% CI, -0.11 to -0.01) to -0.13 mmol/L (95% CI, -0.17 to -0.10) compared with thiazolidinediones, whereas thiazolidinediones were associated with a significant increase in HDL-C compared with placebo (0.09 mmol/L [95% CI, 0.06 to 0.12]). A significant reduction in LDL-C was detected for all GLP-1 RAs versus placebo (range, -0.08 to -0.16 mmol/L), insulin (range, -0.10 to -0.19 mmol/L), and thiazolidinediones (range, -0.16 to -0.24 mmol/L). Exenatide, liraglutide 1.8 mg once daily, and taspoglutide decreased total cholesterol with a range of -0.16 mmol/L (95% CI, -0.26 to -0.06) to -0.27 mmol/L (95% CI, -0.41 to -0.12) versus placebo and thiazolidinediones (range, -0.26 to -0.37 mmol/L). The decreased effect was more evident in exenatide long-acting release and liraglutide 1.8 mg once daily. A significant reduction in triglyceride levels was observed with liraglutide 1.8 mg once daily (-0.30 mmol/L [95% CI, -0.49 to -0.11]) and taspoglutide 20 mg once weekly (-0.17 mmol/L [95% CI, -0.31 to -0.01]) versus placebo.
GLP-1 RAs were associated with modest reductions in LDL-C, total cholesterol, and triglycerides but no significant improvement in HDL-C. Further evidence is needed to determine if improvements in lipid profiles might translate into reductions in cardiovascular outcomes.
本研究旨在评估胰高血糖素样肽-1受体激动剂（GLP-1 RAs）对2型糖尿病患者血脂谱的影响。
检索MEDLINE、Embase、Cochrane图书馆和ClinicalTrials.gov数据库，检索时间从建库至2013年10月31日。选择有可用数据的随机对照试验，条件为比较GLP-1 RAs与安慰剂及传统抗糖尿病药物，疗程≥8周。采用随机效应模型估计血脂谱变化的加权平均差异，并进行网状Meta分析以补充直接比较。
分析纳入了35项涉及13种治疗方法的试验。与噻唑烷二酮类药物相比，GLP-1 RAs使高密度脂蛋白胆固醇（HDL-C）降低，降低幅度在-0.06 mmol/L（95%CI，-0.11至-0.01）至-0.13 mmol/L（95%CI，-0.17至-0.10）之间；而与安慰剂相比，噻唑烷二酮类药物使HDL-C显著升高（0.09 mmol/L [95%CI，0.06至0.12]）。与安慰剂、胰岛素和噻唑烷二酮类药物相比，所有GLP-1 RAs均使低密度脂蛋白胆固醇（LDL-C）显著降低（降低幅度在-0.08至-0.16 mmol/L之间）。与安慰剂相比，艾塞那肽、每日一次1.8 mg的利拉鲁肽和替西帕肽使总胆固醇降低，降低幅度在-0.16 mmol/L（95%CI，-0.26至-0.06）至-0.27 mmol/L（95%CI，-0.41至-0.12）之间，与噻唑烷二酮类药物相比降低幅度在-0.26至-0.37 mmol/L之间。长效释放型艾塞那肽和每日一次1.8 mg的利拉鲁肽的降低效果更明显。与安慰剂相比，每日一次1.8 mg的利拉鲁肽（-0.30 mmol/L [95%CI，-0.49至-0.11]）和每周一次20 mg的替西帕肽（-0.17 mmol/L [95%CI，-0.31至-0.01]）使甘油三酯水平显著降低。
GLP-1 RAs与LDL-C、总胆固醇和甘油三酯的适度降低有关，但对HDL-C无显著改善。需要进一步的证据来确定血脂谱的改善是否能转化为心血管结局的降低。
