Meta-analysis of insulin aspart versus regular human insulin used in a basal–bolus regimen for the treatment of diabetes mellitus (在基础—餐时糖尿病治疗方案中使用门冬胰岛素与使用常规人胰岛素对照研究的Meta分析)

Background:  The objective of the current study was to compare the efficacy of two different insulin formulations, insulin aspart (IAsp) and regular human insulin (RHI), for prandial insulin coverage with neutral protamine Hagedorn (NPH) insulin as basal insulin using a meta-analysis approach. The primary endpoint was change in A1c over time. Secondary endpoints included incidence of hypoglycemia and postprandial glycemic control. Methods Clinical trials (Type 1 and Type 2 diabetes) complying with Good Clinical Practice, and with individual patient data, were included in the meta-analysis. Trials were randomized, consisting of (at least) two treatment arms and had a minimum duration of 12 weeks. Estimates were calculated using fixed-effects and random-effects models. Heterogeneity was assessed for each analysis. The effect of baseline parameters on A1c was analyzed in extended simultaneous models. Results The mean difference in A1c was 0.1% (95% confidence interval [CI] [−0.15; −0.04], P < 0.001) in favor of IAsp. Higher accumulated dose of IAsp, higher age and increased rates of hypoglycemia were associated with improved A1c outcome. Fasting plasma glucose was not significantly different between regimens. Postprandial glucose was significantly lower after treatment with IAsp compared with RHI, but the analysis did present a significant level of heterogeneity (P < 0.001). The overall rate of hypoglycemia was the same with both regimens, but nocturnal hypoglycemia was significantly lower with IAsp. Conclusions:  A basal–bolus regimen with IAsp as bolus insulin provided minimal, but statistically significant, improvement in overall glycemic control with a lower rate of nocturnal hypoglycemic episodes, compared with a corresponding regimen with bolus RHI. 摘要 背景 本研究的目的是使用Meta分析的方法比较两种不同胰岛素制剂的疗效，亦即在联合中性精蛋白锌胰岛素（NPH）作为基础胰岛素的基础上，比较门冬胰岛素（IAsp）与常规人胰岛素（RHI）作为餐时胰岛素的疗效。主要终点是随着时间变化的A1c。次要终点包括低血糖的发生率以及餐后血糖控制情况。 方法 入选Meta分析的临床试验（1型与2型糖尿病）都要遵守临床试验管理规范并且具备每个患者的数据。这些试验都是随机试验，（至少）包含2个治疗组并且持续时间最短为12周。使用固定效应与随机效应模型来计算评估结果。评估每个分析的异质性。在同步扩展模型中分析基线指标对A1c的影响。 结果 A1c的平均差异为0.1%（95% 置信区间[−0.15；−0.04]，P < 0.001），有利于IAsp组。随着A1c 结果的改善，IAsp的总剂量更高、年龄更大并且低血糖发生率更高。两种治疗方案之间的空腹血糖没有显著性差异。与RHI相比较，使用IAsp治疗后餐后血糖发生率显著更低，但是分析显示存在显著的异质性（P < 0.001）。两种治疗方案总的低血糖发生率是一样的，但是IAsp组的夜间低血糖发生率显著更低。 结论 与对应的将RHI作为餐时胰岛素的治疗方案相比较，在基础—餐时治疗方案中将IAsp作为餐时胰岛素后患者的总体血糖控制情况有微小的、但却有显著统计学意义的改善，并且夜间低血糖的发生率也更低。