Garber A J, Wahlen J, Wahl T, Bressler P, Braceras R, Allen E, Jain R
Baylor College of Medicine, Houston, TX 77030, USA.
Diabetes Obes Metab. 2006 Jan;8(1):58-66. doi: 10.1111/j.1463-1326.2005.00563.x.
This observational study in patients with type 2 diabetes failing oral agent therapy with or without basal insulin was conducted to assess whether addition and self-titration of biphasic insulin aspart 70/30 (BIAsp 30) could achieve American Association of Clinical Endocrinologists (AACE)/International Diabetes Federation (IDF) and American Diabetes Association (ADA) glycemic targets (HbA(1c)< or =6.5 and <7%).
Enrolled patients (n = 100, HbA(1c)> or =7.5 and < or =10%) were > or =18 years of age, had diabetes > or =12 months and had received a stable antidiabetic regimen for at least 3 months [minimum of two oral antidiabetic drugs (OADs) or at least one OAD plus once-daily basal insulin < or =60 U]. Patients discontinued prior basal insulin and added one injection of BIAsp 30 (12 U or 70-100% of prior basal insulin dose within 15 min of dinner initiation). Patients self-titrated their BIAsp 30 dose with investigator guidance every 3 or 4 days to achieve pre-breakfast fasting blood glucose (FBG) of 80-110 mg/dl. At 16 weeks, a pre-breakfast injection of 6 U of BIAsp 30 was added if week 15 HbA(1c) exceeded 6.5%; the added dose was titrated to achieve pre-dinner BG of 80-110 mg/dl. After an additional 16 weeks, 3 U of pre-lunch BIAsp 30 was added if HbA(1c) exceeded 6.5%. This added dose was adjusted based on 2-h post-lunch BG to achieve postprandial glucose of 100-140 mg/dl. Subjects achieving an HbA(1c)< or =6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively.
Addition of once-daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA(1c)< or =6.5%) and 41% to achieve ADA targets (HbA(1c) <7%). With two daily injections of BIAsp 30, these glycaemic goals were achieved by 52 and 70% of subjects. With three daily BIAsp 30 injections, 60% of patients achieved HbA(1c)< or =6.5%, and 77% achieved HbA(1c) <7.0%.
This clinical trial demonstrates that initiation of once-daily BIAsp 30 to type 2 diabetes patients poorly controlled on various OAD regimens was an effective treatment approach for achieving glycaemic goals. Additional patients safely achieved these goals by increasing the number of BIAsp 30 injections from one to two, and then, if uncontrolled, from two to three doses per day. Eventually, most patients previously uncontrolled on OADs with or without basal insulin were controlled by the addition and vigorous titration of BIAsp 30 to oral agent therapy.
本观察性研究针对接受或未接受基础胰岛素治疗但口服降糖药治疗失败的2型糖尿病患者，旨在评估添加双相门冬胰岛素70/30（BIAsp 30）并进行自我滴定是否能够实现美国临床内分泌医师协会（AACE）/国际糖尿病联盟（IDF）以及美国糖尿病协会（ADA）的血糖目标（糖化血红蛋白[HbA(1c)]≤6.5%和<7%）。
纳入年龄≥18岁、糖尿病病程≥12个月且接受稳定抗糖尿病治疗方案至少3个月的患者（n = 100，HbA(1c)≥7.5%且≤10%）[至少两种口服降糖药（OADs）或至少一种OAD加每日一次基础胰岛素≤60 U]。患者停用先前的基础胰岛素，并在晚餐开始后15分钟内添加一次BIAsp 30注射（12 U或先前基础胰岛素剂量的70 - 100%）。患者在研究者指导下每3或4天自我滴定BIAsp 30剂量，以使早餐前空腹血糖（FBG）达到80 - 110 mg/dl。在第16周时，如果第15周的HbA(1c)超过6.5%，则添加一次早餐前6 U的BIAsp 30注射；添加的剂量进行滴定以使晚餐前血糖达到80 - 110 mg/dl。再过16周后，如果HbA(1c)超过6.5%，则添加午餐前3 U的BIAsp 30。根据午餐后2小时血糖调整添加的剂量，以使餐后血糖达到100 - 140 mg/dl。在第15周和第31周时HbA(1c)≤6.5%的受试者分别在第16周和第32周完成研究。
晚餐前每日一次添加BIAsp 30使21%的患者实现了AACE和IDF目标（HbA(1c)≤6.5%），41%的患者实现了ADA目标（HbA(1c)<7%）。每日两次注射BIAsp 30时，这些血糖目标分别在52%和70%的受试者中实现。每日三次注射BIAsp 30时，60%的患者HbA(1c)≤6.5%，77%的患者HbA(1c)<7.0%。
本临床试验表明，对于在各种OAD治疗方案下控制不佳的2型糖尿病患者，起始每日一次BIAsp 30是实现血糖目标的有效治疗方法。通过将BIAsp 30注射次数从一次增加到两次，然后在仍未控制时增加到每日三次，更多患者安全地实现了这些目标。最终，大多数先前在OAD治疗下（无论是否使用基础胰岛素）未得到控制的患者，通过在口服药物治疗中添加并积极滴定BIAsp而得到了控制。
