Horvath K, Jeitler K, Berghold A, Ebrahim S H, Gratzer T W, Plank J, Kaiser T, Pieber T R, Siebenhofer A
Medical University Graz, Department of Internal Medicine, Auenbruggerplatz 15, Graz,Austria, 8036.
Cochrane Database Syst Rev. 2007 Apr 18(2):CD005613. doi: 10.1002/14651858.CD005613.pub3.
Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events.
To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus.
Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies.
Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks.
Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed.
Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained.
AUTHORS' CONCLUSIONS: Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.
尽管流行病学试验表明，较高的血糖浓度与发生微血管和大血管并发症的较高风险相关，但降糖治疗对2型糖尿病患者有益的证据存在矛盾。两项大型研究，即英国前瞻性糖尿病研究（UKPDS）和大学组糖尿病项目（UGDP），未发现通过改善代谢控制可降低心血管终点事件。新型胰岛素类似物的理论益处可能会减少大血管和微血管事件。
评估与中性鱼精蛋白锌胰岛素（NPH胰岛素）相比，长效胰岛素类似物（甘精胰岛素和地特胰岛素）长期治疗对2型糖尿病患者的影响。
通过对MEDLINE、EMBASE、Cochrane图书馆进行计算机检索，并与该领域专家以及胰岛素生产公司沟通来获取研究。
纳入的研究需为针对2型糖尿病成年患者的随机对照试验，且试验持续时间至少为24周。
两位作者独立评估试验质量并提取数据。采用随机效应荟萃分析对研究进行汇总。
确定了6项比较甘精胰岛素与NPH（中性鱼精蛋白锌）胰岛素的研究，以及2项比较地特胰岛素与NPH胰岛素的研究。在这些试验中，1715例患者被随机分配至甘精胰岛素组，578例患者被随机分配至地特胰岛素组。纳入试验的持续时间为24至52周。以糖化血红蛋白A1c（HbA1c）作为替代终点来衡量，各治疗组之间的代谢控制及不良反应在临床相关方面并无差异。虽然在任何一项试验中，严重低血糖发生率均未显示出统计学上的显著差异，但接受甘精胰岛素或地特胰岛素治疗的患者出现症状性、总体及夜间低血糖的发生率在统计学上显著更低。未获得长效类似物对死亡率、发病率、生活质量或成本等以患者为导向的结局有有益影响的证据。
我们的分析表明，对于接受“基础”胰岛素治疗的2型糖尿病患者，长效胰岛素类似物治疗若有临床益处，也仅在症状性夜间低血糖事件方面有轻微益处。在获得长期疗效和安全性数据之前，我们建议谨慎使用甘精胰岛素或地特胰岛素进行治疗。
