Attainment of glycaemic goals in type 2 diabetes with once‐, twice‐, or thrice‐daily dosing with biphasic insulin aspart 70/30 (The 1‐2‐3 study)

Abstract

Aim: 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 (HbA1c≤6.5 and <7%). Methods: Enrolled patients (n = 100, HbA1c≥7.5 and ≤10%) were ≥18 years of age, had diabetes ≥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 ≤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 HbA1c 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 HbA1c 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 HbA1c≤6.5% at 15 and 31 weeks completed the study at weeks 16 and 32 respectively. Results: Addition of once‐daily BIAsp 30 before dinner enabled 21% of the patients to achieve AACE and IDF targets (HbA1c≤6.5%) and 41% to achieve ADA targets (HbA1c <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 HbA1c≤6.5%, and 77% achieved HbA1c <7.0%. Conclusions: 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.

Subject‐driven titration of biphasic insulin aspart 30 twice daily is non‐inferior to investigator‐driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open‐label, parallel‐group, multicenter trial

“…As a result of the improved glycemic control, 64.5% patients in subject‐driven group met the HbA 1c target. Effective glycemic control was also reported in other trials where dose adjustment of BIAsp 30 BID was self‐decided by patients13, 14, 15, 16. The reduction of HbA 1c was 1.4–2.5% in those trials, which was similar to that reported in the present study.…”

Comment on: Nauck MA, Duran S, Kim D et al (2007) A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia 50:259–267

“…In this study, insulin dose adjustment was simply left to the investigator. It is not clear from the paper what intensity of follow-up, selfmonitoring, or dose adjustment to what target occurred, but at 52 weeks the premix insulin dose was only 24 U/day, well below doses used in recent studies [4][5][6][7][8], and below doses normally encountered in clinical practice. This appeared not to be the result of hypoglycaemia in this particular group of patients-the reported hypoglycaemia rate was as low with insulin as with the glucagon-like peptide-1 mimetic.…”

“…The result of this is that the blood glucose control achieved was relatively poor in the insulin-treated group (a fall of 0.9% in HbA 1c from a baseline of 8.6%) when compared with nearly all recently published treat-to-target studies with insulin therapy in people with type 2 diabetes [4][5][6][7][8]. In these, final HbA 1c is typically <7.0% (achieved by 68% of participants in the INITIATE study [5], and eventually by 77% of participants in the 1-2-3 study, where a third premix injection was an option) [6].…”

“…In these, final HbA 1c is typically <7.0% (achieved by 68% of participants in the INITIATE study [5], and eventually by 77% of participants in the 1-2-3 study, where a third premix injection was an option) [6]. The LanMet study achieved an HbA 1c of 7.1%, but this was from baseline levels of 9.1% [8].…”

Optimal glucose control in type 2 diabetes mellitus—a guide for the family practitioner

“…The newer insulin analogue mixed insulins seem, however, to give even better results if given three times per day immediately before meals. 55 Glycaemic control can also be achieved by the administration of basal insulin (NPH / Isophane / Glargine / Detemir 56 ) with mealtime boluses (Aspart/ Glulisine), which allows the greatest flexibility with regard to eating habits. This is also known as the basal bolus regimen.…”