Baylor College of Medicine, Houston, TX, USA.
Lancet. 2012 Apr 21;379(9825):1498-507. doi: 10.1016/S0140-6736(12)60205-0.
Basal insulin therapy does not stop loss of β-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess efficacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus.
In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged ≥18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA(1c)) of 7·0-10·0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratified by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3·9-<5·0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA(1c) from baseline to week 52 (non-inferiority limit of 0·4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00972283.
744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58·9 years [SD 9·3], diabetes duration 13·5 years [7·3], HbA(1c) 8·3% [0·8], and fasting plasma glucose 9·2 mmol/L [3·1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA(1c) decreased by 1·1% in the degludec group and 1·2% in the glargine group (estimated treatment difference [degludec-glargine] 0·08%, 95% CI -0·05 to 0·21), confirming non-inferiority. Rates of overall confirmed hypoglycaemia (plasma glucose <3·1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11·1 vs 13·6 episodes per patient-year of exposure; estimated rate ratio 0·82, 95% CI 0·69 to 0·99; p=0·0359), as were rates of nocturnal confirmed hypoglycaemia (1·4 vs 1·8 episodes per patient-year of exposure; 0·75, 0·58 to 0·99; p=0·0399). Rates of severe hypoglycaemia seemed similar (0·06 vs 0·05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of differences. Rates of other adverse events did not differ between groups.
A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine.
Novo Nordisk.
基础胰岛素治疗并不能阻止β细胞功能的丧失，这是 2 型糖尿病的标志，因此糖尿病的控制不可避免地会恶化。胰岛素德古胰岛素是一种新型的超长效基础胰岛素。我们旨在评估与胰岛素甘精相比，胰岛素德古胰岛素在 2 型糖尿病患者中的疗效和安全性。
在这项为期 52 周、3 期、开放标签、以目标为导向、非劣效性试验中，我们在 12 个国家的 123 个地点招募了年龄在 18 岁及以上的成年人（患有 2 型糖尿病，糖化血红蛋白（HbA1c）在 3 个月或更长时间内为 7.0-10.0%，使用任何胰岛素方案（无论是否使用口服抗糖尿病药物）。我们通过中央交互式反应系统，按以前的胰岛素方案将符合条件的参与者以 3:1 的比例随机分配接受每日一次皮下注射德古胰岛素或甘精胰岛素。基础胰岛素滴定至早餐前自我测量的血浆葡萄糖浓度 3.9-<5.0mmol/L。主要终点是通过方差分析在全分析集中测量德古胰岛素对甘精胰岛素的非劣效性，HbA1c 从基线到第 52 周的变化（非劣效性界限为 0.4%）。我们评估了所有治疗患者的低血糖发生率。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT00972283。
744（99%）名随机分配德古胰岛素的 755 名参与者和 248（99%）名随机分配甘精胰岛素的 251 名参与者被纳入全分析集（平均年龄 58.9 岁[标准差 9.3]，糖尿病病程 13.5 年[7.3]，HbA1c 8.3%[0.8]，空腹血浆葡萄糖 9.2mmol/L[3.1]）；618（82%）和 211（84%）名参与者完成了试验。一年后，德古胰岛素组 HbA1c 下降 1.1%，甘精胰岛素组下降 1.2%（德古胰岛素-甘精胰岛素估计治疗差异 0.08%，95%CI-0.05 至 0.21），证实了非劣效性。德古胰岛素组总体确证性低血糖（血浆葡萄糖<3.1mmol/L 或需要协助的严重发作）发生率低于甘精胰岛素组（11.1 比 13.6 例患者年暴露；估计率比 0.82，95%CI 0.69 至 0.99；p=0.0359），夜间确证性低血糖发生率也较低（1.4 比 1.8 例患者年暴露；0.75，0.58 至 0.99；p=0.0399）。严重低血糖的发生率似乎相似（德古胰岛素和甘精胰岛素组分别为 0.06 比 0.05 例患者年暴露），但发生率太低，无法评估差异。两组其他不良事件发生率无差异。
对于晚期 2 型糖尿病患者，为降低低血糖及其后果的风险而采取的次优糖尿病控制策略可能是不必要的，因为新型基础胰岛素（如德古胰岛素）与甘精胰岛素相比，低血糖风险较低。
诺和诺德。
