Yale Jean-François, Pettus Jeremy Hodson, Brito-Sanfiel Miguel, Lavalle-Gonzalez Fernando, Merino-Trigo Ana, Stella Peter, Chevalier Soazig, Buzzetti Raffaella
Department of Medicine, McGill University, Montreal, Canada.
Department of Endocrinology, University of California, San Diego, United States of America.
PLoS One. 2018 Jan 25;13(1):e0190579. doi: 10.1371/journal.pone.0190579. eCollection 2018.
To evaluate the effect of concomitant dipeptidyl peptidase IV inhibitor (DPPIVi) use on efficacy and safety of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with type 2 diabetes on oral antihyperglycaemic drugs.
A post hoc patient-level meta-analysis was performed using data from EDITION 2 (basal insulin [N = 811]) and EDITION 3 (insulin-naïve [N = 878]), multicentre, randomised, open-label, parallel-group, phase 3a trials of similar design. Endpoints analysed included HbA1c, hypoglycaemia and adverse events, investigated in subgroups of participants with and without concomitant DPPIVi use.
Of 1689 participants randomised, 107 (13%, Gla-300) and 133 (16%, Gla-100) received DPPIVi therapy. The least squares mean change in HbA1c (baseline to month 6) was comparable between treatment groups, irrespective of DPPIVi use (no evidence of heterogeneity of treatment effect across subgroups, p = 0.753), although group sizes were unbalanced. The cumulative mean number of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemic events, and the risk and annualised rate of such events, were consistently lower for Gla-300 than Gla-100 during the night (between 00:00 and 05:59 h) or at any time of day (24 h period), irrespective of DPPIVi use. Severe hypoglycaemia occurred in 8/838 and 10/844 participants in the Gla-300 and Gla-100 groups, respectively, and was not affected by DPPIVi use. The adverse event profile was similar between treatment groups and DPPIVi subgroups.
Glycaemic control with Gla-300 was comparable to Gla-100, with less hypoglycaemia during the night and at any time of day (24 h), irrespective of concomitant DPPIVi use.
ClinicalTrials.gov NCT01499095; NCT01676220.
评估在使用口服降糖药的2型糖尿病患者中，联合使用二肽基肽酶IV抑制剂（DPPIVi）对300 U/mL甘精胰岛素（Gla-300）与100 U/mL甘精胰岛素（Gla-100）疗效和安全性的影响。
使用来自设计相似的多中心、随机、开放标签、平行组3a期试验EDITION 2（基础胰岛素[N = 811]）和EDITION 3（初治胰岛素[N = 878]）的数据进行事后患者水平的荟萃分析。分析的终点包括糖化血红蛋白、低血糖和不良事件，在联合使用和未联合使用DPPIVi的参与者亚组中进行研究。
在1689名随机分组的参与者中，107名（13%，Gla-300）和133名（16%，Gla-100）接受了DPPIVi治疗。无论是否使用DPPIVi，各治疗组之间糖化血红蛋白（基线至第6个月）的最小二乘均值变化相当（各亚组治疗效果无异质性证据，p = 0.753），尽管组间规模不均衡。在夜间（00:00至05:59 h）或一天中的任何时间（24小时期间），无论是否使用DPPIVi，Gla-300组确诊的（≤3.9 mmol/L [≤70 mg/dL]）或严重低血糖事件的累积平均数量、此类事件的风险和年化发生率始终低于Gla-100组。Gla-300组和Gla-100组分别有8/838和10/844名参与者发生严重低血糖，且不受DPPIVi使用的影响。各治疗组和DPPIVi亚组之间的不良事件情况相似。
无论是否联合使用DPPIVi，Gla-300的血糖控制效果与Gla-100相当，且夜间和一天中任何时间（24小时）的低血糖发生率更低。
ClinicalTrials.gov NCT01499095；NCT01676220。
