Department of Endocrinology, Diabetes, and Metabolism, MedStar Health Research Institute, Hyattsville, MD 20782, USA.
Clin Ther. 2012 Jun;34(6):1247-1258.e22. doi: 10.1016/j.clinthera.2012.04.013. Epub 2012 May 18.
Considerable clinical data on the treatment of type 2 diabetes with incretin-based therapies (glucagon-like peptide 1 receptor agonists [GLP-1RAs] and dipeptidyl-peptidase IV [DPP-4] inhibitors) are available.
This meta-analysis was performed to support the understanding of the overall evidence by summarizing the findings from studies of the incretin-based therapies.
The MEDLINE, EMBASE, BIOSIS, and BIOSIS trial databases were searched for relevant literature published between January 1, 1990, and June 30, 2011. Search terms included GLP-1, DPP-4, the names of drugs that have been approved by the US Food and Drug Administration for the treatment of diabetes, and the names of drugs that have not been approved but are in late-stage research. Studies were included if they were randomized controlled trials of 12 to 52 weeks' duration and having change from baseline in hemoglobin (Hb) A(1c) as the primary end point. The random effects meta-analyses models examined HbA(1c), fasting plasma glucose (FPG), and body weight for individual therapies, but did not compare effects between therapies.
The reviewers identified 362 unique clinical studies, of which 80 were eligible for inclusion in the present meta-analysis. Mean baseline HbA(1c) values ranged from 7.4% to 10.3% (GLP-1RA studies) and 7.2% to 9.3% (DPP-4 inhibitor studies). The highest maintenance doses of the GLP-1RAs and the DPP-4 inhibitors were associated with changes from baseline in mean HbA(1c) of -1.1% to -1.6% and -0.6% to -1.1%, respectively. Mean reductions in FPG with exenatide once weekly (QW) or liraglutide once daily were apparently greater than those with exenatide twice daily (BID) and the DPP-4 inhibitors, with the exception of vildagliptin. Mean weight losses with the GLP-1RAs and the DPP-4 inhibitors were >-2.0 and -0.2 to -0.6 kg, respectively. The limitations of the present analysis included a lack of adjustment for placebo use and interstudy heterogeneity associated with differences in methodology (eg, management of concurrent medications, blinding, criteria for treatment discontinuation).
All of the incretin-based therapies in the present meta-analysis were associated with significant reductions from baseline in HbA(1c) and FPG. Further direct comparative studies between the GLP-1RAs and the DPP-4 inhibitors and within the GLP-1RA class are justified.
目前有大量关于使用肠促胰岛素类药物（胰高血糖素样肽 1 受体激动剂 [GLP-1RA] 和二肽基肽酶 4 [DPP-4] 抑制剂）治疗 2 型糖尿病的临床数据。
本荟萃分析旨在通过总结肠促胰岛素类药物研究结果，支持对整体证据的理解。
检索 MEDLINE、EMBASE、BIOSIS 和 BIOSIS 试验数据库，获取 1990 年 1 月 1 日至 2011 年 6 月 30 日期间发表的相关文献。检索词包括 GLP-1、DPP-4、美国食品和药物管理局批准用于治疗糖尿病的药物名称以及处于后期研究阶段但尚未获得批准的药物名称。纳入的研究为持续 12 至 52 周、以血红蛋白（Hb）A1c 较基线的变化为主要终点的随机对照试验。随机效应荟萃分析模型考察了各治疗药物的 HbA1c、空腹血糖（FPG）和体重，但未比较各治疗药物之间的疗效。
审查人员共识别出 362 项独特的临床研究，其中 80 项符合纳入本荟萃分析的条件。基线 HbA1c 值范围为 7.4%至 10.3%（GLP-1RA 研究）和 7.2%至 9.3%（DPP-4 抑制剂研究）。GLP-1RA 和 DPP-4 抑制剂的最大维持剂量与 HbA1c 较基线的平均变化分别为-1.1%至-1.6%和-0.6%至-1.1%。每周一次艾塞那肽或每日一次利拉鲁肽与每日两次艾塞那肽和 DPP-4 抑制剂相比，空腹血糖的平均降低幅度明显更大，除维格列汀外。GLP-1RA 和 DPP-4 抑制剂的平均体重减轻量分别为＞-2.0kg 和-0.2kg 至-0.6kg。本分析的局限性包括未调整安慰剂的使用以及研究间异质性，异质性与方法学差异有关（如，同时用药的管理、盲法、停药标准）。
本荟萃分析中的所有肠促胰岛素类药物均与 HbA1c 和 FPG 较基线的显著降低相关。GLP-1RA 和 DPP-4 抑制剂之间以及 GLP-1RA 类药物内部的直接比较研究是合理的。
