Associates in Internal Medicine, Chicago, Illinois 60611, USA.
Clin Ther. 2011 Jul;33(7):874-83. doi: 10.1016/j.clinthera.2011.05.093. Epub 2011 Jul 8.
The Initiation of Insulin to reach A1C Target (INITIATEplus) trial studied the effect of self-titrating biphasic insulin aspart 70/30 (BiAsp 30) twice daily during 24 weeks in insulin-naïve patients with type 2 diabetes who were poorly controlled by oral medication, and originally randomized according to frequency of dietary counseling interventions.
The purpose of this study was to compare the efficacy and tolerability of biphasic insulin aspart 70/30 (BIAsp 30, NovoLog Mix 70/30) in INITIATEplus patients ≤65 versus >65 years old, irrespective of dietary counseling frequency, and to test the hypothesis that self-titrating BIAsp 30 in patients >65 years old could be well-tolerated and effective in this age group.
An exploratory post hoc subanalysis, using standard statistical methods, was performed on patients stratified according to age. Data collected from 3492 patients in the intent-to-treat population who were ≤65 years old and 716 patients who were >65 years old compared glycosylated hemoglobin (HbA(1c)) and plasma glucose changes from baseline. Hypoglycemia rates and adverse event (AE) incidence were compared for the tolerability population of 4007 patients ≤65 years old and 805 patients >65 years old.
Baseline-adjusted HbA(1c) changes for patients ≤65 versus >65 years old were -2.38% versus -2.73% (P < 0.0001), with final HbA(1c) achieving 7.55% and 7.06%, respectively. Thirty-nine percent of patients ≤65 years old achieved HbA(1c) ≤7% compared with 51% of patients >65 years old. Baseline-adjusted fasting plasma glucose decreases were greater for the >65 year old population (85.2 vs 91.2 mg/dL; P = 0.004; ≤65 vs >65 years old, respectively). Minor hypoglycemia was reported in 9.7% and 7.7% of patients ≤65 versus >65 years old, respectively (0.52 vs 0.41 episodes per patient per year [ppy]; P = 0.01). Major hypoglycemia occurred in 1.5% and 3.1% of patients (0.05 vs 0.14 episodes ppy, ≤65 vs >65 years old, respectively; P < 0.0001). Nocturnal major hypoglycemia was reported for 0.4% and 0.6% of patients (P = 0.0028), whereas nocturnal minor hypoglycemia was reported for 3.8% and 2.6% (P = 0.007) of patients ≤65 and >65 years old, respectively. AEs were reported for 24% and 28% of patients ≤65 and >65 years old, respectively, serious AEs were reported for 4% and 9% of patients, respectively, and AE-related withdrawals were reported for 1.3% and 2% of patients, respectively.
Self-titrated biphasic insulin aspart 70/30 was found to be well-tolerated and effective in type 2 diabetes patients >65 years old, as well as in patients ≤65 years old. HbA(1c) and fasting plasma glucose decreases were significantly (P < 0.05) higher for patients >65 years old versus patients ≤65 years old. Tolerability was indicated by major and minor hypoglycemia rates at or below <0.5 episodes ppy in both age groups. Overall rates of AE and serious AEs were higher among patients > 65 years; withdrawals related to AEs were 2% compared with 1.3% in the younger age group.
胰岛素起始达标研究（INITIATEplus）旨在研究在口服药物控制不佳的 2 型糖尿病患者中，每日两次给予门冬胰岛素 70/30 预混制剂（BiAsp 30）的自我滴定效果，这些患者为胰岛素初治者，试验最初根据膳食咨询干预的频率随机分组。
本研究旨在比较在 INITIATEplus 患者中，不论膳食咨询干预的频率如何，每日两次给予门冬胰岛素 70/30（BIAsp 30，诺和锐 30）的疗效和耐受性，并且验证在年龄＞65 岁的患者中自我滴定 BIAsp 30 是安全且有效的假设。
对按年龄分层的意向治疗人群中的 3492 例≤65 岁和 716 例＞65 岁患者进行探索性事后亚组分析，采用标准统计方法，评估糖化血红蛋白（HbA1c）和从基线的血浆葡萄糖变化。对 4007 例≤65 岁和 805 例＞65 岁的可耐受人群进行低血糖发生率和不良事件（AE）发生率的比较。
≤65 岁与＞65 岁患者的基线调整后 HbA1c 变化分别为-2.38%和-2.73%（P＜0.0001），最终 HbA1c 分别达到 7.55%和 7.06%。39%的≤65 岁患者达到 HbA1c≤7%，而＞65 岁患者为 51%。＞65 岁患者的空腹血浆葡萄糖降低更显著（85.2 与 91.2 mg/dL；P=0.004；≤65 与＞65 岁，分别）。≤65 岁与＞65 岁患者的低血糖发生率分别为 9.7%和 7.7%（0.52 与 0.41 例次/患者/年；P=0.01）。低血糖发生率分别为 1.5%和 3.1%（0.05 与 0.14 例次/患者/年；P＜0.0001）。分别有 0.4%和 0.6%的患者报告夜间严重低血糖（P=0.0028），而夜间轻微低血糖发生率分别为 3.8%和 2.6%（P=0.007）。≤65 岁和＞65 岁患者的 AEs 发生率分别为 24%和 28%，严重 AEs 发生率分别为 4%和 9%，AE 相关停药率分别为 1.3%和 2%。
在年龄＞65 岁和≤65 岁的 2 型糖尿病患者中，自我滴定的门冬胰岛素 70/30 被证明是安全且有效的，与≤65 岁患者相比，＞65 岁患者的 HbA1c 和空腹血浆葡萄糖降低更显著（P＜0.05）。在两个年龄组中，低血糖发生率均＜0.5 例次/患者/年，提示具有良好的耐受性。＞65 岁患者的 AE 和严重 AE 发生率较高，与 AE 相关的停药率为 2%，而在年轻患者中为 1.3%。
