Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial

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• 作者：Dr ; Prof Alan J Garber ; MD^a ; ^{agarber@bcm.tmc.edu} ; Allen B King ; MD^b ; Prof Stefano Del Prato ; MD^c ; Seamus Sreenan ; MD^d ; Mustafa K Balci ; MD^e ; Prof Manuel Muñ ; oz-Torres ; MD^f ; Prof Julio Rosenstock ; MD^g ; Lars A Endahl ; PhD^h ; Ann Marie Ocampo Francisco ; MD^h ; Priscilla Hollander ; MDⁱ ; on behalf of the NN1250-3582 (BEGIN BB T2D) Trial Investigators^&Dagger ;
• 刊名：The Lancet
• 出版年：2012
• 期刊代码：182_01406736
• 类别：med
• 出版时间：21-27 April, 2012
• 卷：379
• 期：9825
• 页码：1498-1507
• 文件大小：283 K

摘要

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Summary

Background

Basal insulin therapy does not stop loss of 尾-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.

Methods

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 鈮?8 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA_1c) of 7路0-10路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路9-<5路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路4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with , number .

Findings

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路9 years [SD 9路3], diabetes duration 13路5 years [7路3], HbA_1c 8路3%[0路8], and fasting plasma glucose 9路2 mmol/L [3路1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA_1c decreased by 1路1%in the degludec group and 1路2%in the glargine group (estimated treatment difference [degludec-glargine] 0路08%, 95%CI 鈭?路05 to 0路21), confirming non-inferiority. Rates of overall confirmed hypoglycaemia (plasma glucose <3路1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11路1 vs 13路6 episodes per patient-year of exposure; estimated rate ratio 0路82, 95%CI 0路69 to 0路99; p=0路0359), as were rates of nocturnal confirmed hypoglycaemia (1路4 vs 1路8 episodes per patient-year of exposure; 0路75, 0路58 to 0路99; p=0路0399). Rates of severe hypoglycaemia seemed similar (0路06 vs 0路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.

Interpretation

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.

Funding

Novo Nordisk.