Lower rates of hypoglycemia during maintenance treatment with insulin degludec/insulin aspart versus biphasic insulin aspart 30: a combined analysis of two Phase 3a studies in type 2 diabetes

• Published in: Journal of diabetes Vol. 8; no. 5; pp. 720 - 728
• Main Authors: Christiansen, Jens Sandahl, Niskanen, Leo, Rasmussen, Søren, Johansen, Thue, Fulcher, Greg
• Format: Journal Article
• Language: English
• Published: Australia Blackwell Publishing Ltd 01.09.2016; John Wiley & Sons, Inc
• Subjects: 2型糖尿病; Aged; b.i.d. treatment; b.i.d.治疗; biphasic insulin aspart 30; Biphasic Insulins - adverse effects; Biphasic Insulins - therapeutic use; Blood Glucose - metabolism; Clinical Trials, Phase III as Topic; Confidence intervals; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Administration Schedule; Female; Glycated Hemoglobin A - metabolism; Humans; Hypoglycemia; Hypoglycemia - blood; Hypoglycemia - chemically induced; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Insulin Aspart - adverse effects; Insulin Aspart - therapeutic use; insulin degludec/insulin aspart; Insulin, Isophane - adverse effects; Insulin, Isophane - therapeutic use; Insulin, Long-Acting - adverse effects; Insulin, Long-Acting - therapeutic use; Maintenance Chemotherapy; Male; Middle Aged; Multicenter Studies as Topic; Outcome Assessment (Health Care) - methods; Outcome Assessment (Health Care) - statistics & numerical data; Randomized Controlled Trials as Topic; Risk Factors; type 2 diabetes; 低血糖; 双相门冬胰岛素30; 德谷胰岛素/门冬胰岛素; insulin degludec/insulin aspart; type 2 diabetes; b.i.d.治疗; 德谷胰岛素/门冬胰岛素; hypoglycemia; b.i.d. treatment; 双相门冬胰岛素30; biphasic insulin aspart 30; 低血糖; 2型糖尿病
• ISSN: 1753-0393; 1753-0407
• DOI: 10.1111/1753-0407.12355

Background Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid‐acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30). Methods Hypoglycemia data were analyzed from two similarly designed randomized controlled open‐label treat‐to‐target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal. Results Over 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between‐treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; −31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; −62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; −84%; P = 0.0061), respectively. Conclusions Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin. 摘要 背景: 德谷胰岛素/门冬胰岛素(Insulin degludec/insulin aspart,IDegAsp)是一种可溶性的制剂,它是由基础胰岛素类似物‐德谷胰岛素与速效餐时胰岛素‐门冬胰岛素构成的单一注射制剂。当前这项由2个3a期试验构成的联合分析对比了参与者每日2次使用IDegAsp或者双相门冬胰岛素30(biphasic insulin aspart 30,BIAsp 30)治疗后的低血糖发生率。 方法: 分析所用的低血糖数据来自于两项设计同似的、随机对照、开放标签的成年2型糖尿病患者达标治疗的3a期临床试验。参与者每日两次使用IDegAsp或者BIAsp 30治疗,在早餐以及晚上主餐时注射。 结果: 经过26周之后,IDegAsp组(n = 504)与BIAsp 30组(n = 364)相比,经过证实的全部低血糖、经过证实的夜间低血糖以及严重低血糖事件的发生率分别减少了19%、57%与39%;估算的低血糖发生率比值比分别为0.81(95%可信区间[CI]为0.67,0.98;P = 0.0341)、0.43(95% CI为0.31,0.59;P = 0.0001)与0.61(95% CI为0.26,1.45;P = NS)。在维持治疗期间治疗组之间的差异就更加明显了(≥ 16周);与BIAsp 30组相比,IDegAsp组经过证实的全部低血糖、经过证实的夜间低血糖以及严重低血糖事件的发生率比值分别为0.69(95% CI为0.55,0.87;‐31%;P = 0.0015);0.38(95% CI为0.25,0.58;‐62%;P < 0.0001)与0.16(95% CI为0.04,0.59;‐84%;P = 0.0061)。 结论: 在既往使用胰岛素治疗的2型糖尿病受试者中,与每日2次注射BIAsp 30相比,每日2次注射IDegAsp后改善血糖控制程度相类似,但是低血糖的风险却更低,特别是夜间低血糖。