Monami Matteo, Dicembrini Ilaria, Nreu Besmir, Andreozzi Francesco, Sesti Giorgio, Mannucci Edoardo
Diabetology, Careggi Teaching Hospital, Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50141, Florence, Italy.
Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
Acta Diabetol. 2017 Dec;54(12):1101-1114. doi: 10.1007/s00592-017-1054-2. Epub 2017 Sep 20.
The aim of the present meta-analysis is the identification of the characteristics of patients, which predict the efficacy on HbA1c of glucagon-like peptide-1 receptor agonists (GLP-1 RA).
A Medline and Embase search for "exenatide" OR "liraglutide" OR "albiglutide" OR "dulaglutide" OR "lixisenatide" was performed, collecting randomized clinical trials (duration > 12 weeks) up to September 2016, comparing GLP-1 RA at the maximal approved dose with placebo or active drugs. Furthermore, unpublished studies were searched in the www.clinicaltrials.gov register. For meta-analyses, the outcome considered were 24- and 52-week HbA1c. Separate analyses were performed, whenever possible, for subgroups of trials based on several inclusion criteria. In addition, meta-regression analyses were performed for comparisons for which 10 or more trails were available.
A total of 92 trials fulfilling the inclusion criteria were identified. In placebo-controlled trials (n = 41), the 24-week mean reduction of HbA1c with GLP-1 RA was - 0.75 [- 0.87; - 0.63]%. Shorter-acting molecules appear to be more effective in patients with lower fasting glucose, whereas longer-acting agents in patients with higher fasting hyperglycaemia. Obesity and duration of diabetes do not seem to moderate the efficacy of GLP-1 RA, whereas in non-Caucasians and older patients liraglutide could be less effective. At 52 weeks, only 9 placebo-controlled trials were available for preventing any reliable analyses.
Using a variety of approaches (meta-analyses of subgroup of trials, meta-regression, systematic review of subgroup analyses in individual trials, and meta-analyses of subgroups of patients), we identified some putative predictors of efficacy of GLP-1 RA, which deserve further investigation.
本荟萃分析旨在确定可预测胰高血糖素样肽-1受体激动剂（GLP-1 RA）对糖化血红蛋白（HbA1c）疗效的患者特征。
检索Medline和Embase数据库，搜索词为“艾塞那肽”或“利拉鲁肽”或“阿必鲁肽”或“度拉鲁肽”或“利司那肽”，收集截至2016年9月的随机临床试验（持续时间>12周），比较最大批准剂量的GLP-1 RA与安慰剂或活性药物。此外，在www.clinicaltrials.gov注册库中搜索未发表的研究。对于荟萃分析，所考虑的结局指标为24周和52周时的HbA1c。只要有可能，就根据多个纳入标准对试验亚组进行单独分析。此外，对于有10项或更多试验可用的比较进行了荟萃回归分析。
共确定了92项符合纳入标准的试验。在安慰剂对照试验（n = 41）中，GLP-1 RA使HbA1c在24周时的平均降低幅度为-0.75 [-0.87；-0.63]%。短效分子似乎对空腹血糖较低的患者更有效，而长效制剂对空腹血糖较高的患者更有效。肥胖和糖尿病病程似乎不会影响GLP-1 RA的疗效，而在非白种人和老年患者中，利拉鲁肽的效果可能较差。在52周时，仅有9项安慰剂对照试验可用于进行任何可靠的分析。
通过多种方法（试验亚组的荟萃分析、荟萃回归、对单个试验中亚组分析的系统评价以及患者亚组的荟萃分析），我们确定了一些GLP-1 RA疗效的假定预测因素，值得进一步研究。
