The development of basal insulin analogues has reduced the risk of hypoglycaemia in insulin-treated individuals with type 2 diabetes. Insulin degludec and insulin glargine 300 U/ml (glargine U300) represent an evolution of basal insulin analogues, both of them reducing the risk of hypoglycaemia as compared with that associated with glargine U100. However, whether degludec and glargine U300 are equivalent with respect to glycaemic control and risk of hypoglycaemia remains to be fully ascertained. In the CONCLUDE trial, 1609 individuals with type 2 diabetes were randomised to either degludec 200 U/ml (degludec U200) or glargine U300. In this issue of Diabetologia (https://doi.org/10.1007/s00125-019-05080-9) the investigators report that during the maintenance period, HbA1c improved to a similar extent in the two groups with no significant difference in the rate of overall hypoglycaemia (the primary endpoint of the study), while rates of nocturnal symptomatic and severe hypoglycaemia (secondary endpoints) were lower with degludec U200 than with glargine U300. These results, although of great interest to the clinician, need to be carefully interpreted as they cannot be considered as conclusive. First, the primary endpoint was not met and, therefore, analyses of secondary endpoints remain exploratory. Even assuming that degludec is superior to glargine in reducing the risk of hypoglycaemia, the mechanism(s) accounting for such an advantage remain elusive and potential differences in pharmacokinetics and pharmacodynamics difficult to appreciate because of methodological issues. The study design had to be amended because of lack of reliability of the glucometers initially used in the trial, particularly in the low blood glucose ranges, so the potential implications of these changes in the subsequent conduct of the trial cannot be excluded. Finally, comparison with the BRIGHT trial, the only other available head-to-head study, is complicated by differences between the two studies in the primary endpoint (HbA1c reduction vs reduction of the risk of hypoglycaemia), study population (insulin-experienced vs insulin-naive) and concomitant glucose-lowering medications. In spite of all this, CONCLUDE teaches us an important lesson regarding the need, particularly in the clinical setting, to monitor the reliability of the glucometers the diabetic individual uses to adjust his/her insulin dose. Insufficient precision or inappropriate use of the glucometer can easily offset any minute advantage a new insulin can offer with respect to glycaemic control and risk of hypoglycaemia.

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CONCLUDE试验的结论性如何？

基础胰岛素类似物的发展降低了接受胰岛素治疗的2型糖尿病患者发生低血糖的风险。地高胰岛素和300 U / ml甘精胰岛素（甘精胰岛素U300）代表了基础胰岛素类似物的发展，与甘精胰岛素U100相比，它们都降低了低血糖的风险。然而，在控制血糖和低血糖的风险方面，degludec和甘精氨酸U300是否等效，仍有待充分确定。在CONCLUDE试验中，将1609名2型糖尿病患者随机分配为地高地松200 U / ml（degludec U200）或甘精胰岛素U300。在本期《糖尿病》（https://doi.org/10.1007/s00125-019-05080-9）中，研究人员报告说，在维护期间，两组的HbA1c改善程度相似，总体低血糖发生率（研究的主要终点）无显着差异，而地格曲松U200的夜间症状和严重低血糖发生率（次要终点）低于甘精胰岛素U300 。这些结果尽管使临床医生非常感兴趣，但由于不能被认为是结论性的，因此需要仔细解释。首先，没有达到主要终点，因此，对次要终点的分析仍然是探索性的。甚至假设在降低降低低血糖的风险方面，地格列本优于甘精胰岛素，仍可说明这种优势的机理仍然不清楚，并且由于方法学问题，药理动力学和药效学的潜在差异也难以理解。由于最初用于试验的血糖仪缺乏可靠性，尤其是在低血糖范围内，因此必须对研究设计进行修改，因此不能排除这些变化对后续试验的潜在影响。最后，与BRIGHT试验（仅有的其他可用的头对头研究）进行比较，这是由于两项研究在主要终点（HbA1c降低与低血糖风险的降低），研究人群（胰岛素经历的vs初次使用胰岛素）和降糖药物。尽管如此，结论仍然教会了我们重要的一课，特别是在临床环境中，以监测糖尿病患者用来调整他/她的胰岛素剂量的血糖仪的可靠性。