一项 28 周、随机、多中心、开放性、平行分组的 III 期临床试验，旨在研究双相门冬胰岛素 70 每日三次注射与双相门冬胰岛素 30 每日两次注射在 2 型糖尿病患者中的疗效和安全性。

28-week, randomized, multicenter, open-label, parallel-group phase III trial to investigate the efficacy and safety of biphasic insulin aspart 70 thrice-daily injections vs twice-daily injections of biphasic insulin aspart 30 in patients with type 2 diabetes.

机构信息

Department of Diabetes and Metabolic Diseases, The University of Tokyo.

Development Division, Novo Nordisk Pharma Ltd., Tokyo.

出版信息

J Diabetes Investig. 2010 Jun 1;1(3):103-10. doi: 10.1111/j.2040-1124.2010.00015.x.

DOI:10.1111/j.2040-1124.2010.00015.x

PMID:24843416

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4008024/

Abstract

UNLABELLED

Aims/Introduction: An insulin analogue formulation with a 7:3 ratio of rapid-acting and intermediate-acting fractions, biphasic insulin aspart 70 (BIAsp70) was developed to supplement basal insulin between meals and mimic the physiological pattern of postprandial insulin secretion.

MATERIALS AND METHODS

We carried out a randomized, open-label study to compare the efficacy and safety profiles of BIAsp70 and an insulin analogue formulation with a 3:7 ratio of rapid-acting and intermediate-acting fractions (BIAsp30) in type 2 diabetes mellitus patients. Patients were randomized and received either thrice-daily BIAsp70 (n = 145) or twice-daily BIAsp30 (n = 144) for 28 weeks. The primary end-point was glycated hemoglobin (HbA1c) after 16 weeks of treatment.

RESULTS

Non-inferiority of BIAsp70 vs BIAsp30 was confirmed and superiority was established with a between-group difference (BIAsp70-BIAsp30) in HbA1c after 16 weeks of treatment of -0.35% (95% CI: -0.51 to -0.19; P < 0.0001 for superiority). The mean postprandial glucose increment (19.96 vs 54.35 mg/dL; P < 0.0001) and M-value (12.99 vs 17.94; P < 0.0001) at 16 weeks were smaller in the BIAsp70 group than in the BIAsp30 group, and were maintained at 28 weeks. Pre-breakfast glucose (157.9 vs 140.7 mg/dL), total insulin dose (46.8 vs 38.1 U/day) and weight gain (+1.94 vs 1.23 kg) at week 28 were greater in the BIAsp70 group. Incidence of nocturnal hypoglycemia was significantly lower with BIAsp70 vs BIAsp30 (1.23 vs 3.21 events/subject year; P = 0.0002) at week 28.

CONCLUSIONS

Thrice-daily BIAsp70 was superior to twice-daily BIAsp30 in terms of HbA1c change, with less variation in daytime plasma glucose profiles. BIAsp70 was well tolerated, with a lower incidence of nocturnal hypoglycemia vs BIAsp30. This trial was registered with ClinicalTrial.gov (no. NCT00318786). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2010.00015.x, 2010).

摘要

目的/引言：一种快速作用和中效作用比例为 7:3 的胰岛素类似物制剂，即双相门冬胰岛素 70（BIAsp70），旨在补充餐间基础胰岛素，并模拟餐后胰岛素分泌的生理模式。

材料和方法

我们进行了一项随机、开放标签研究，比较了 2 型糖尿病患者中 BIAsp70 与快速作用和中效作用比例为 3:7 的胰岛素类似物制剂（BIAsp30）的疗效和安全性。患者随机接受每日 3 次 BIAsp70（n=145）或每日 2 次 BIAsp30（n=144）治疗 28 周。主要终点是治疗 16 周后的糖化血红蛋白（HbA1c）。

结果

证实了 BIAsp70 与 BIAsp30 的非劣效性，并建立了治疗 16 周后 HbA1c 的组间差异（BIAsp70-BIAsp30）为 -0.35%（95%CI：-0.51 至-0.19；P<0.0001 用于优势）。BIAsp70 组治疗 16 周时餐后血糖升高（19.96 与 54.35mg/dL；P<0.0001）和 M 值（12.99 与 17.94；P<0.0001）均小于 BIAsp30 组，且在 28 周时仍保持不变。治疗 28 周时，BIAsp70 组空腹前血糖（157.9 与 140.7mg/dL）、总胰岛素剂量（46.8 与 38.1U/天）和体重增加（+1.94 与 1.23kg）均较高。BIAsp70 组夜间低血糖发生率明显低于 BIAsp30 组（1.23 与 3.21 事件/受试者年；P=0.0002）。

结论

BIAsp70 在 HbA1c 变化方面优于 BIAsp30，日间血糖谱波动较小。BIAsp70 耐受性良好，夜间低血糖发生率低于 BIAsp30。本试验在 ClinicalTrials.gov 注册（编号：NCT00318786）。（糖尿病调查杂志，doi:10.1111/j.2040-1124.2010.00015.x，2010）。