AIMS/HYPOTHESIS A head-to-head randomised trial was conducted to evaluate hypoglycaemia safety with insulin degludec 200 U/ml (degludec U200) and insulin glargine 300 U/ml (glargine U300) in individuals with type 2 diabetes treated with basal insulin. METHODS This randomised (1:1), open-label, treat-to-target, multinational trial included individuals with type 2 diabetes, aged ≥18 years with HbA1c ≤80 mmol/mol (9.5%) and BMI ≤45 kg/m2. Participants were previously treated with basal insulin with or without oral glucose-lowering drugs (excluding insulin secretagogues) and had to fulfil at least one predefined criterion for hypoglycaemia risk. Both degludec U200 and glargine U300 were similarly titrated to a fasting blood glucose target of 4.0-5.0 mmol/l. Endpoints were assessed during a 36 week maintenance period and a total treatment period up to 88 weeks. There were three hypoglycaemia endpoints: (1) overall symptomatic hypoglycaemia (either severe, an event requiring third-party assistance, or confirmed by blood glucose [<3.1 mmol/l] with symptoms); (2) nocturnal symptomatic hypoglycaemia (severe or confirmed by blood glucose with symptoms, between 00:01 and 05:59 h); and (3) severe hypoglycaemia. The primary endpoint was the number of overall symptomatic hypoglycaemic events in the maintenance period. Secondary hypoglycaemia endpoints included the number of nocturnal symptomatic events and number of severe hypoglycaemic events during the maintenance period. RESULTS Of the 1609 randomised participants, 733 of 805 (91.1%) in the degludec U200 arm and 734 of 804 (91.3%) in the glargine U300 arm completed the trial (87.3% and 87.8% completed on treatment, respectively). Baseline characteristics were comparable between the two treatment arms. For the primary endpoint, the rate of overall symptomatic hypoglycaemia was not significantly lower with degludec U200 vs glargine U300 (rate ratio [RR] 0.88 [95% CI 0.73, 1.06]). As there was no significant difference between treatments for the primary endpoint, the confirmatory testing procedure for superiority was stopped. The pre-specified confirmatory secondary hypoglycaemia endpoints were analysed using pre-specified statistical models but were now considered exploratory. These endpoints showed a lower rate of nocturnal symptomatic hypoglycaemia (RR 0.63 [95% CI 0.48, 0.84]) and severe hypoglycaemia (RR 0.20 [95% CI 0.07, 0.57]) with degludec U200 vs glargine U300. CONCLUSIONS/INTERPRETATION There was no significant difference in the rate of overall symptomatic hypoglycaemia with degludec U200 vs glargine U300 in the maintenance period. The rates of nocturnal symptomatic and severe hypoglycaemia were nominally significantly lower with degludec U200 during the maintenance period compared with glargine U300. TRIAL REGISTRATION ClinicalTrials.gov NCT03078478 FUNDING: This trial was funded by Novo Nordisk (Bagsvaerd, Denmark).

中文翻译：

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在接受胰岛素治疗的2型糖尿病患者中，使用地德格列克胰岛素和甘精胰岛素U300发生低血糖的风险：随机对照研究。

目的/假设进行了一项头对头随机试验，以评估在用基础胰岛素治疗的2型糖尿病患者中，使用地格胰岛素200 U / ml（degludec U200）和甘精胰岛素300 U / ml（甘精胰岛素U300）进行低血糖安全性的评估。方法这项随机（1：1），开放标签，靶向治疗的跨国试验包括年龄≥18岁，HbA1c≤80mmol / mol（9.5％）和BMI≤45kg / m2的2型糖尿病患者。参与者先前接受过基础胰岛素治疗，有或没有口服降糖药（不包括胰岛素促分泌剂），并且必须满足至少一项预先确定的低血糖风险标准。将degludec U200和甘精氨酸U300相似地滴定至空腹血糖目标值4.0-5.0 mmol / l。在36周的维持期内以及长达88周的总治疗期内评估了终点。低血糖存在三个终点：（1）总体症状性低血糖（严重，需要第三方协助的事件，或经血糖[<3.1 mmol / l]并伴有症状的确证）；（2）夜间症状性低血糖症（严重或经血糖确诊并伴有症状，在00:01至05:59 h之间）；（3）严重的低血糖症。主要终点是维持期内总体症状性降血糖事件的数量。继发性低血糖的终点包括维持期间的夜间症状事件数量和严重的低血糖事件数量。结果在1609名随机参与者中，在degludec U200臂中有805名中的733名（91.1％）和804名中的734名（91。甘精氨酸U300臂中的3％完成了试验（分别完成了87.3％和87.8％的治疗）。两个治疗组之间的基线特征相当。对于主要终点，地格列酮U200和甘精胰岛素U300的总症状性低血糖发生率没有显着降低（比率[RR] 0.88 [95％CI 0.73，1.06]）。由于主要终点治疗之间无显着差异，因此终止了优越性的确证性测试程序。使用预先确定的统计模型对预先确定的确认性继发性低血糖终点进行了分析，但现在被认为是探索性的。这些终点显示地格列酮U200与甘精胰岛素U300相比，夜间症状性低血糖发生率较低（RR 0.63 [95％CI 0.48，0.84]）和严重低血糖发生率（RR 0.20 [95％CI 0.07，0.57]）。结论/解释在维持期内，degludec U200 vs glargine U300的总体症状性低血糖发生率无显着差异。与甘精胰岛素U300相比，在维持期内，地格列酮U200的夜间症状性和严重低血糖发生率在名义上显着降低。试验注册ClinicalTrials.gov NCT03078478资金：该试验由Novo Nordisk（丹麦巴格斯韦德）资助。