Amori Renee E, Lau Joseph, Pittas Anastassios G
Division of Endocrinology, Diabetes and Metabolism, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
JAMA. 2007 Jul 11;298(2):194-206. doi: 10.1001/jama.298.2.194.
Pharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined.
To assess the efficacy and safety of incretin-based therapy in adults with type 2 diabetes based on randomized controlled trials published in peer-reviewed journals or as abstracts.
We searched MEDLINE (1966-May 20, 2007) and the Cochrane Central Register of Controlled Trials (second quarter, 2007) for English-language randomized controlled trials involving an incretin mimetic (glucagonlike peptide 1 [GLP-1] analogue) or enhancer (dipeptidyl peptidase 4 [DPP4] inhibitor). We also searched prescribing information, relevant Web sites, reference lists and citation sections of recovered articles, and abstracts presented at recent conferences.
Randomized controlled trials were selected if they were at least 12 weeks in duration, compared incretin therapy with placebo or other diabetes medication, and reported hemoglobin A(1c) data in nonpregnant adults with type 2 diabetes.
Two reviewers independently assessed trials for inclusion and extracted data. Differences were resolved by consensus. Meta-analyses were conducted for several efficacy and safety outcomes.
Of 355 potentially relevant articles identified, 51 were retrieved for detailed evaluation and 29 met the inclusion criteria. Incretins lowered hemoglobin A(1c) compared with placebo (weighted mean difference, -0.97% [95% confidence interval {CI}, -1.13% to -0.81%] for GLP-1 analogues and -0.74% [95% CI, -0.85% to -0.62%] for DPP4 inhibitors) and were noninferior to other hypoglycemic agents. Glucagonlike peptide 1 analogues resulted in weight loss (1.4 kg and 4.8 kg vs placebo and insulin, respectively) while DPP4 inhibitors were weight neutral. Glucagonlike peptide 1 analogues had more gastrointestinal side effects (risk ratio, 2.9 [95% CI, 2.0-4.2] for nausea and 3.2 [95% CI, 2.5-4.4] for vomiting). Dipeptidyl peptidase 4 inhibitors had an increased risk of infection (risk ratio, 1.2 [95% CI, 1.0-1.4] for nasopharyngitis and 1.5 [95% CI, 1.0-2.2] for urinary tract infection) and headache (risk ratio, 1.4 [95% CI, 1.1-1.7]). All but 3 trials had a 30-week or shorter duration; thus, long-term efficacy and safety could not be evaluated.
Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes, with modest efficacy and a favorable weight-change profile. Careful postmarketing surveillance for adverse effects, especially among the DPP4 inhibitors, and continued evaluation in longer-term studies and in clinical practice are required to determine the role of this new class among current pharmacotherapies for type 2 diabetes.
增强肠促胰岛素途径的药物疗法最近已可获得，但它们在2型糖尿病管理中的作用尚未明确界定。
基于发表在同行评审期刊上或作为摘要的随机对照试验，评估以肠促胰岛素为基础的疗法在成年2型糖尿病患者中的疗效和安全性。
我们检索了MEDLINE（1966年至2007年5月20日）和Cochrane对照试验中央注册库（2007年第二季度），以查找涉及肠促胰岛素类似物（胰高血糖素样肽1[GLP-1]类似物）或增强剂（二肽基肽酶4[DPP4]抑制剂）的英文随机对照试验。我们还检索了处方信息、相关网站、检索到的文章的参考文献列表和引用部分，以及近期会议上发表的摘要。
如果随机对照试验持续时间至少为12周，将肠促胰岛素疗法与安慰剂或其他糖尿病药物进行比较，并报告非妊娠成年2型糖尿病患者的糖化血红蛋白A1c数据，则选择这些试验。
两名评审员独立评估试验是否纳入并提取数据。差异通过协商解决。对几个疗效和安全性结果进行了荟萃分析。
在确定的355篇可能相关的文章中，检索到51篇进行详细评估，29篇符合纳入标准。与安慰剂相比，肠促胰岛素可降低糖化血红蛋白A1c（GLP-1类似物的加权平均差异为-0.97%[95%置信区间{CI}，-1.13%至-0.81%]，DPP4抑制剂为-0.74%[95%CI，-0.85%至-0.62%]），且不劣于其他降糖药物。胰高血糖素样肽1类似物导致体重减轻（分别比安慰剂和胰岛素减轻1.4kg和4.8kg），而DPP4抑制剂对体重无影响。胰高血糖素样肽1类似物有更多胃肠道副作用（恶心的风险比为2.9[95%CI，2.0-4.2]，呕吐的风险比为3.2[95%CI，2.5-4.4]）。二肽基肽酶4抑制剂感染风险增加（鼻咽炎的风险比为1.2[95%CI，1.0-1.4]，尿路感染的风险比为1.5[95%CI，1.0-2.2]）和头痛（风险比为1.4[95%CI，1.1-1.7]）。除3项试验外，所有试验的持续时间均为30周或更短；因此，无法评估长期疗效和安全性。
对于非妊娠成年2型糖尿病患者，肠促胰岛素疗法为目前可用的降糖药物提供了一种替代选择，疗效适中且体重变化情况良好。需要对不良反应进行仔细的上市后监测，尤其是在DPP4抑制剂中，并在长期研究和临床实践中持续评估，以确定这一新类别在当前2型糖尿病药物治疗中的作用。
