Analogue advances in glycaemic control: Novo Nordisk highlights the therapeutic value of insulin aspart
Lois Jovanovic, Santa Barbara, USA
This year’s EASD seminar provided a good opportunity for Novo Nordisk to convey its ongoing commitment to product development in the field of diabetes. In a symposium highlighting the need for therapies that keep pace with emerging knowledge, the increasing clinical evidence in favour of its rapid-acting insulin analogue, insulin aspart (NovoRapid), was high on the agenda.
After opening the discussion with a brief history of insulin preparations, Professor Lois Jovanovic (Santa Barbara, CA, USA) summarized the increasing evidence that improved glycaemic control reduces adverse outcomes in patients with both Type 1 and Type 2 diabetes. The shortfall between ideal glycaemic control and that achieved in clinical practice is, however, still significant; tight metabolic control continues to be jeopardized by the lifestyle restrictions and hypoglycaemic risk associated with intensified therapy using conventional insulins.
Dr Peter Kurtzhals (Novo Nordisk, Denmark) reported on the computer-assisted modelling strategies employed in the development of Novo Nordisk’s insulin analogues — the soluble basal insulin analogue insulin detemir, still in development, and rapid-acting insulin aspart.
Professor Stephen Colagiuri (New South Wales, Australia) explained how, by virtue of reduced self-association properties, insulin aspart can be used in basal-bolus regimens to recreate plasma insulin profiles that approximate the physiological norm. Absorption of insulin aspart is rapid and its duration of action short-lived, allowing convenient immediate pre-meal dosing and achieving greater serum concentrations in a shorter time than is possible with soluble human insulin.
Professor Eberhard Standl (Münich, Germany) described how such a profile targets the postprandial glucose excursion, shown in large epidemiological studies to be a more accurate predictor of diabetic cardiovascular complications and death than fasting glucose or HbA1c. Historically, emphasis has been placed on reducing HbA1c and fasting glucose; postprandial control has only recently become a specific target for therapy. The disappointing impact that treatments to date have had on mortality may reflect this failure to target the postprandial aspect of glycaemic control.
Professor Stephen Colagiuri (Randwick, Australia) underlined the value of insulin aspart in achieving superior long-term metabolic control and greater response rates in Type 1 diabetic patients in studies of >6 months’ duration (Fig. 1).
1: Long-term glycaemic control is better with insulin aspart than
soluble human insulin (n>1900)
Insulin aspart reduces HbA1c but, importantly, not at the expense of increased hypoglycaemic risk.
The value of a treatment that improves metabolic control whilst retaining an acceptable adverse event profile is widely recognized. Professor Stephanie Amiel (London, UK) highlighted the concept of the glycaemic control spectrum, demonstrated in both the Diabetes Control and Complications Trial and the United Kingdom Prospective Diabetes Study, in which there appeared to be no value for HbA1c below which patient prognosis could not be improved by further reduction. The greatest obstacle to attaining idealized glycaemic control remains the high incidence of major hypoglycaemia associated with intensive therapy. By coordinating mealtime insulin availability with physiological demand, insulin aspart is designed to minimize the limitations of existing insulins. Basal-bolus therapy using insulin aspart has been shown to incur a lower risk of major hypoglycaemia than soluble human insulin at any level of glycaemic control. Furthermore, asymptomatic nocturnal hypoglycaemia is significantly reduced (Fig. 2) — a clinically important consideration given the likely association between nocturnal hypoglycaemia and the development of hypoglycaemic unawareness.
2: Risk of major nocturnal hypoglycaemia in patients with Type 1
diabetes, in long term studies (n>1900)
The use of insulin aspart in a basal bolus or insulin pump regimen requires algorithms for both insulin components. In order to get the full advantage of insulin aspart, its use demands manipulation of the basal component, highlighted Dr Robert Ratner (Washington DC, USA).
Treatment guidelines for NovoRapid recommend that most patients can be switched onto NovoRapid from soluble human insulin on a unit-for-unit basis. Clinical evidence suggests that this can reduce HbA1c and postprandial glucose levels, lower hypoglycaemic risk and provide a more convenient injection regimen than is possible with soluble human insulin. Insulin aspart has already shown encouraging results, and it is hoped that the success of this product will continue to benefit patients, whilst raising awareness of the advantages of insulin analogues.