注射用胰高血糖素样肽-1（GLP-1）受体激动剂与口服二肽基肽酶-4（DPP-4）抑制剂和钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂的安慰剂反应：一项系统评价和荟萃分析。
The placebo response of injectable GLP-1 receptor agonists vs. oral DPP-4 inhibitors and SGLT-2 inhibitors: a systematic review and meta-analysis.
作者信息
de Wit Helena M, Te Groen Maarten, Rovers Maroeska M, Tack Cees J
机构信息
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
Departments of Operating Rooms and Health Evidence, Radboud University Medical Center, Nijmegen, the Netherlands.
出版信息
Br J Clin Pharmacol. 2016 Jul;82(1):301-14. doi: 10.1111/bcp.12925. Epub 2016 Apr 22.
AIMS
The size of the placebo response in type 2 diabetes (T2DM) treatment and its relation to the route of drug administration have not been systematically reviewed. We aimed to determine weight loss, change in HbA1c and incidence of adverse events after treatment with injectable placebo GLP-1 receptor agonist (GLP-1ra), compared with oral placebo DPP-4 inhibitor (DPP-4i) and placebo SGLT-2 inhibitor (SGLT-2i).
METHODS
PubMed, EMBASE and Central were searched up to September 2014 for randomized placebo controlled trials investigating GLP-1ra, DPP-4i or SGLT2-i. Data on placebo groups were extracted and pooled using a generic inverse variance random effects model.
RESULTS
Sixty-seven trials were included, involving 2522, 5290 and 2028 patients randomized to placebo GLP-1ra, placebo DPP-4i and placebo SGLT-2i, respectively. Body weight decreased by -0.67 kg (95% CI -1.03, -0.31) after treatment with placebo GLP-1ra (-0.76 kg [95% CI -1.10, -0.43] with placebo short acting GLP-1ra and -0.32 kg [95% CI -1.75, 1.10] with placebo long acting GLP-1ra) and by -0.31 kg (95% CI -0.64, 0.01) with placebo DPP-4i (P = 0.06 for difference with placebo short acting GLP-1ra). Placebo SGLT-2i resulted in an intermediate -0.48 kg (95% CI -0.81, -0.15) weight loss. Weight loss with placebo showed a strong correlation with the active comparator drug (r(2) = 0.40-0.78). HbA1c changed little with placebo treatment (-0.23%, 0.10% and -0.13% for placebo GLP-1ra, DPP-4i and SGLT-2i). Adverse events occurred frequently with placebo, were often similar to the active comparator drug and led to drop-out in 2.0-2.7% of cases.
CONCLUSIONS
The response to placebo treatment was related to its active comparator, with injectable placebo GLP-1ra showing a relevant response on weight, whereas oral placebo DPP4i showed no significant response. These findings may suggest that subjective expectations influence T2DM treatment efficacy, which can possibly be employed therapeutically.
目的
2型糖尿病（T2DM）治疗中安慰剂反应的大小及其与药物给药途径的关系尚未得到系统评价。我们旨在确定与口服安慰剂二肽基肽酶4抑制剂（DPP-4i）和安慰剂钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2i）相比，注射用安慰剂胰高血糖素样肽-1受体激动剂（GLP-1ra）治疗后的体重减轻、糖化血红蛋白（HbA1c）变化及不良事件发生率。
方法
检索截至2014年9月的PubMed、EMBASE和CENTRAL数据库，查找调查GLP-1ra、DPP-4i或SGLT-2i的随机安慰剂对照试验。使用通用逆方差随机效应模型提取并汇总安慰剂组的数据。
结果
纳入67项试验，分别有2522、5290和2028例患者被随机分配至安慰剂GLP-1ra、安慰剂DPP-4i和安慰剂SGLT-2i组。安慰剂GLP-1ra治疗后体重下降-0.67 kg（95%CI -1.03，-0.31）（短效安慰剂GLP-1ra组体重下降-0.76 kg[95%CI -1.10，-0.43]，长效安慰剂GLP-1ra组体重下降-0.32 kg[95%CI -1.75，1.10]），安慰剂DPP-4i组体重下降-0.31 kg（95%CI -0.64，0.01）（与短效安慰剂GLP-1ra组相比差异P = 0.06）。安慰剂SGLT-2i导致体重减轻0.48 kg（95%CI -0.81，-0.15），处于中间水平。安慰剂导致的体重减轻与活性对照药物有很强的相关性（r² = 0.40 - 0.78）。安慰剂治疗后HbA1c变化不大（安慰剂GLP-1ra、DPP-4i和SGLT-2i组分别为-0.23%、0.10%和-0.13%）。安慰剂治疗时不良事件频繁发生，常与活性对照药物相似，导致2.0 - 2.7%的病例退出研究。
结论
对安慰剂治疗的反应与其活性对照药物有关，注射用安慰剂GLP-1ra在体重方面有显著反应，而口服安慰剂DPP-4i无显著反应。这些发现可能表明主观期望会影响T2DM的治疗效果，这可能具有治疗应用价值。
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