Siebenhofer A, Plank J, Berghold A, Jeitler K, Horvath K, Narath M, Gfrerer R, Pieber T R
Leopold Auenbrugger Medical University of Graz, University of Medicine, Auenbruggerplatz 15, Graz, Austria, 8036.
Cochrane Database Syst Rev. 2006 Apr 19(2):CD003287. doi: 10.1002/14651858.CD003287.pub4.
Short acting insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates.
To assess the effects of short acting insulin analogues versus regular human insulin.
The Cochrane Library (Issue 3, 2005), MEDLINE, EMBASE until September 2005.
Randomised controlled trials with an intervention duration of at least 4 weeks.
Trial selection and evaluation of study quality was done independently by two reviewers.
Altogether 8274 participants took part in 49 randomised controlled studies. Most studies were of poor methodological quality. In patients with type 1 diabetes, the weighted mean difference (WMD) of HbA1c was -0.1% (95% CI: -0.2 to -0.1) in favour of insulin analogue, whereas in patients with type 2 diabetes the WMD was 0.0% (95% CI: -0.1 to 0.0). In subgroup analyses of different types of interventions in type 1 diabetic patients, the WMD in HbA1c was -0.2% (95% CI: -0.3 to -0.1) in favour of insulin analogue in studies using continuous subcutaneous insulin injections (CSII), whereas for conventional intensified insulin therapy (IIT) studies the WMD in HbA1c was -0.1% (95% CI: -0.1 to 0.0). The WMD of the overall mean hypoglycaemic episodes per patient per month was -0.2 (95% CI: -1.1 to 0.7) and -0.2 (95% CI: -0.5 to 0.1) for analogues in comparison to regular insulin in patients with type 1 diabetes and type 2 diabetes, respectively. For studies in type 1 diabetes patients the incidence of severe hypoglycaemia ranged from 0 to 247.3 (median 21.8) episodes per 100 person-years for insulin analogues and from 0 to 544 (median 46.1) for regular insulin, in type 2 the incidence ranged from 0 to 30.3 (median 0.3) episodes per 100 person-years for insulin analogues and from 0 to 50.4 (median 1.4) for regular insulin. No study was designed to investigate possible long term effects (e.g. mortality, diabetic complications), in particular in patients with diabetes related complications.
AUTHORS' CONCLUSIONS: Our analysis suggests only a minor benefit of short acting insulin analogues in the majority of diabetic patients treated with insulin. Until long term efficacy and safety data are available we suggest a cautious response to the vigorous promotion of insulin analogues. For safety purposes, we need a long-term follow-up of large numbers of patients and well designed studies in pregnant women to determine the safety profile for both the mother and the unborn child.
正如许多科学辩论所反映的那样，糖尿病患者使用短效胰岛素类似物仍存在争议。
评估短效胰岛素类似物与常规人胰岛素的效果。
检索截至2005年9月的考克兰图书馆（2005年第3期）、MEDLINE、EMBASE。
干预持续时间至少4周的随机对照试验。
由两名评价员独立进行试验选择和研究质量评估。
共有8274名参与者参加了49项随机对照研究。大多数研究的方法学质量较差。在1型糖尿病患者中，糖化血红蛋白（HbA1c）的加权平均差（WMD）为-0.1%（95%可信区间：-0.2至-0.1），有利于胰岛素类似物；而在2型糖尿病患者中，WMD为0.0%（95%可信区间：-0.1至0.0）。在1型糖尿病患者不同类型干预的亚组分析中，在使用持续皮下胰岛素注射（CSII）的研究中，HbA1c的WMD为-0.2%（95%可信区间：-0.3至-0.1），有利于胰岛素类似物；而对于传统强化胰岛素治疗（IIT）研究，HbA1c的WMD为-0.1%（95%可信区间：-0.1至0.0）。与常规胰岛素相比，1型糖尿病和2型糖尿病患者中胰岛素类似物每位患者每月总体平均低血糖发作次数的WMD分别为-0.2（95%可信区间：-1.1至0.7）和-0.2（95%可信区间：-0.5至0.1）。对于1型糖尿病患者的研究，胰岛素类似物每100人年严重低血糖发生率为0至247.3（中位数21.8）次，常规胰岛素为0至544（中位数46.1）次；在2型糖尿病中，胰岛素类似物每100人年发生率为0至30.3（中位数0.3）次，常规胰岛素为0至50.4（中位数1.4）次。没有研究设计用于调查可能的长期影响（如死亡率、糖尿病并发症），特别是在患有糖尿病相关并发症的患者中。
我们的分析表明，在大多数接受胰岛素治疗的糖尿病患者中，短效胰岛素类似物仅有微小益处。在获得长期疗效和安全性数据之前，我们建议对胰岛素类似物的大力推广持谨慎态度。出于安全目的，我们需要对大量患者进行长期随访，并对孕妇进行精心设计的研究，以确定对母亲和未出生胎儿的安全性。
