University of Sheffield, Sheffield, UK. s.heller@sheffi eld.ac.uk
Lancet. 2012 Apr 21;379(9825):1489-97. doi: 10.1016/S0140-6736(12)60204-9.
Intensive basal-bolus insulin therapy has been shown to improve glycaemic control and reduce the risk of long-term complications that are associated with type 1 diabetes mellitus. Insulin degludec is a new, ultra-longacting basal insulin. We therefore compared the efficacy and safety of insulin degludec and insulin glargine, both administered once daily with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes.
In an open-label, treat-to-target, non-inferiority trial, undertaken at 79 sites (hospitals and centres) in six countries, adults (aged ≥18 years) with type 1 diabetes (glycated haemoglobin [HbA(1c)] ≤10% [86 mmol/mol]), who had been treated with basal-bolus insulin for at least 1 year, were randomly assigned in a 3:1 ratio, with a computer-generated blocked allocation sequence, to insulin degludec or insulin glargine without stratification by use of a central interactive response system. The primary outcome was non-inferiority of degludec to glargine, assessed as a reduction in HbA(1c) after 52 weeks, with the intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00982228.
Of 629 participants, 472 were randomly assigned to insulin degludec and 157 to insulin glargine; all were analysed in their respective treatment groups. At 1 year, HbA(1c) had fallen by 0·40% points (SE 0·03) and 0·39% points (0·07), respectively, with insulin degludec and insulin glargine (estimated treatment difference -0·01% points [95% CI -0·14 to 0·11]; p<0·0001 for non-inferiority testing) and 188 (40%) and 67 (43%) participants achieved a target HbA(1c) of less than 7% (<53 mmol/mol). Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe) were similar in the insulin degludec and insulin glargine groups (42·54 vs 40·18 episodes per patient-year of exposure; estimated rate ratio [degludec to glargine] 1·07 [0·89 to 1·28]; p=0·48). The rate of nocturnal confirmed hypoglycaemia was 25% lower with degludec than with glargine (4·41 vs 5·86 episodes per patient-year of exposure; 0·75 [0·59 to 0·96]; p=0·021). Overall serious adverse event rates (14 vs 16 events per 100 patient-years of exposure) were similar for the insulin degludec and insulin glargine groups.
Insulin degludec might be a useful basal insulin for patients with type 1 diabetes because it provides effective glycaemic control while lowering the risk of nocturnal hypoglycaemia, which is a major limitation of insulin therapy.
Novo Nordisk.
强化基础-餐时胰岛素治疗已被证明可改善血糖控制并降低与 1 型糖尿病相关的长期并发症风险。德谷胰岛素是一种新型的超长效基础胰岛素。因此，我们比较了德谷胰岛素和甘精胰岛素在 1 型糖尿病基础-餐时胰岛素治疗中的疗效和安全性，两种胰岛素均联合餐时门冬胰岛素使用。
在一项于六个国家的 79 个地点（医院和中心）进行的、开放标签、目标导向、非劣效性试验中，纳入了至少接受过 1 年基础-餐时胰岛素治疗的、年龄≥18 岁的 1 型糖尿病（糖化血红蛋白[HbA1c]≤10%[86mmol/mol]）成人患者，他们被随机以 3:1 的比例分配，使用计算机生成的分组区组随机分配，无分层，使用中央互动反应系统，接受德谷胰岛素或甘精胰岛素治疗。主要结局是德谷胰岛素非劣效于甘精胰岛素，评估为 52 周时 HbA1c 的降低，意向治疗分析。该试验在 ClinicalTrials.gov 注册，编号为 NCT00982228。
在 629 名参与者中，472 名随机分配至德谷胰岛素组，157 名随机分配至甘精胰岛素组；所有患者均在各自的治疗组中进行分析。在 1 年时，HbA1c 分别下降了 0.40%点（SE 0.03）和 0.39%点（0.07），德谷胰岛素组和甘精胰岛素组的估计治疗差异为-0.01%点（95%CI-0.14 至 0.11；p<0.0001 用于非劣效性检验），188（40%）和 67（43%）名参与者达到了 HbA1c 小于 7%（<53mmol/mol）的目标。总体确证性低血糖（血浆葡萄糖<3.1mmol/L 或严重）的发生率在德谷胰岛素组和甘精胰岛素组相似（42.54 比 40.18 例患者-年的暴露事件；估计的治疗比值比[德谷胰岛素比甘精胰岛素]为 1.07[0.89 至 1.28]；p=0.48）。德谷胰岛素组夜间确证性低血糖的发生率比甘精胰岛素组低 25%（4.41 比 5.86 例患者-年的暴露事件；0.75[0.59 至 0.96]；p=0.021）。德谷胰岛素组和甘精胰岛素组的总体严重不良事件发生率（100 患者-年的暴露事件中分别为 14 和 16 例事件）相似。
德谷胰岛素可能是 1 型糖尿病患者有用的基础胰岛素，因为它在降低夜间低血糖风险的同时提供了有效的血糖控制，而夜间低血糖是胰岛素治疗的一个主要限制。
诺和诺德。
