Science of premix insulin: where have we reached?

Abstract

Diabetes is a progressive disease and by achieving and maintaining optimal glycemic control, the onset of complications can be prevented or delayed. Insulin is most effective at any stage of diabetes. Although basal-bolus therapy is the gold standard treatment, it has its own limitations such as multiple pricks, close monitoring and cost. Premixed insulin on the other hand is convenient, requires fewer injections, is a single device and delivers both the basal and bolus component till the next meal. Although premixed insulin analogs have the advantages of mealtime flexibility, compliance and better post-prandial glucose control, no significant differences have been observed in HbA1c reduction and overall hypoglycemia when compared to premixed human insulin. This review will attempt to analyze the efficacy, safety and limitations of currently available premix human insulin and premix analogs including recent advancements in the area.

Keywords:

• BHI 30
• BIAsp 30
• IDegAsp
• premixed insulins

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Basal only therapy is definitely a more convenient option requiring less monitoring; however, it does not adequately address prandial glycemic increment. Moreover, absence of a short-acting component is a barrier for insulin intensification further in the course of therapy. Premix formulations largely take care of this prandial issue.

• Unfortunately, the classical pharmacokinetic/pharmacodynamic profiles of the individual rapid-acting (bolus) component and long-acting (basal) component are also not retained when these are premixed and this implies to all existing premix insulin formulation containing protamine. This also imparts the disadvantage of the so called ‘shoulder effect’ as discussed. Another issue with the prefixed formulation could be reduced flexibility especially seen during self-titration.

• Basal-bolus therapy closely mimics the physiological insulin secretion but poses a problem when it comes to patient compliance due to increased number of pricks, not only for administration of insulin but also for self-monitoring.

• Currently available insulin analog therapies possibly offer better prandial glycemic control and better safety profile in particular with nocturnal hypoglycemia, when compared to conventional human insulin therapies but the challenges of daytime hypoglycemia are largely still not addressed.

• There is future scope for the development of newer insulin that will cover the existing unmet needs and IDegAsp co-formulation seems to be one such promising option but its limitations and cost–effectiveness will only be known after its long-term usage.