Ten years of experience with biphasic insulin aspart 30: from drug development to the latest clinical findings

Abstract

Biphasic insulin aspart 30 (BIAsp 30) includes 30% soluble rapid-acting insulin aspart (IAsp) along with an intermediate-acting 70% protaminated IAsp that provides coverage of prandial and basal insulin in a single injection. As BIAsp 30 has been available internationally for 10 years, this review provides a comprehensive overview of the discovery of BIAsp 30, its pharmacokinetic and pharmacodynamic profile, safety and efficacy outcomes from the clinical trial programme, 'real-life' clinical insights provided by observational study data, and cost effectiveness and quality-of-life information. These studies have demonstrated that BIAsp 30 once or twice daily is an appropriate option for insulin initiation. BIAsp 30 also provides a switch option in patients on biphasic human insulin (BHI). Switching from BHI to BIAsp 30 is associated with improved postprandial glucose (PPG) and reduced nocturnal and major hypoglycaemia, although daytime hypoglycaemia is higher with BIAsp 30. Intensification of BIAsp 30 can be achieved by increasing the number of daily doses up to three times daily with meals. Therefore, BIAsp 30 provides an intensification option for individuals who are not achieving control with basal insulin and would prefer the simplicity of a single biphasic insulin instead of progressing to a basal-bolus approach. BIAsp 30 has a simple dose-titration algorithm, which enables patients to effectively self-titrate their insulin dose. Cost-effectiveness analyses have demonstrated that BIAsp 30 is cost effective or dominant compared with BHI 30 or insulin glargine in a number of healthcare settings. In conclusion, BIAsp 30 offers a simple and flexible option for insulin initiation and intensification that provides coverage of both fasting and prandial glucose.

Fig. 1

Dissociation of insulin hexamers following subcutaneous injection. Reproduced from Brange et al.,[12] with permission from the American Diabetes Association. © 1990 American Diabetes Association.

Fig. 2

Insulin aspart differs from human insulin by the single amino-acid substitution of a proline by an aspartic acid residue at B28. Reproduced from Brange et al.,[12] with permission from the American Diabetes Association. © 1990 American Diabetes Association.

Fig. 3

Pharmacokinetics and pharmacodynamics of biphasic insulin aspart 30 and biphasic human insulin 30. (a) Serum insulin concentration (reproduced from Jacobsen et al.,[17] with kind permission from Springer Science+Business Media). (b) Insulin action (reproduced from Weyer et al.,[16] with permission from the American Diabetes Association. © 1997 American Diabetes Association). BHI = biphasic human insulin; BIAsp = biphasic insulin aspart; * p < 0.0001.

Fig. 4

Comparison of plasma insulin profiles of twice-daily biphasic insulin aspart 30 and once-daily insulin glargine. Reproduced from Hermansen et al.,[21] with kind permission from Springer Science+Business Media. © 2006 Springer. BIAsp = biphasic insulin aspart.

Fig. 5

Meta-analyses of post-treatment differences in postprandial glucose (mg/dL) between insulin aspart 30/70 and (a) long-acting insulin analogues[–32] and (b) biphasic human insulin.[–35] Reproduced from Qayyum et al.[28]

Fig. 6

Meta-analysis of major hypoglycaemia in patients with type 2 diabetes mellitus treated with biphasic insulin aspart 30 or biphasic human insulin 30.[21,28,33,35] Reproduced from Davidson et al.,[29] with permission from Elsevier. © 2009 Elsevier. BIAsp = biphasic human insulin; BIAsp = biphasic insulin aspart.

Table I

Biphasic insulin aspart 30 compared with biphasic human insulin in type 2 diabetes

Table II

Biphasic insulin aspart 30 compared with basal insulin in type 2 diabetes

Table III

Key trials of BIAsp 30 in insulin-naive patients

Table IV

Results from the IMPROVE™ study^a

Table V

Results from the PRESENT™ study^a

Table VI

Cost effectiveness of biphasic insulin aspart 30 compared with insulin glargine^a

Table VII

Cost effectiveness of biphasic insulin aspart 30 vs human insulin^a