Pharmakologische Eigenschaften des schneller wirksamen Insulins aspart (Faster-acting Insulin aspart)

Zusammenfassung

Faster-acting Insulin aspart ist eine durch die Zugabe der als sicher geltenden Hilfsstoffe Niacinamid und L-Arginin weiterentwickelte Formulierung zu Insulin aspart (IAsp). Die gepoolte Auswertung von sechs pharmakologischen Studien im randomisierten Crossover-Design bei erwachsenen Menschen mit Typ-1-Diabetes ergab für die subkutane Injektion von Faster-acting Insulin aspart 0,2 E/kg ein um ca. 5 Minuten früheres erstes Auftreten von Insulin im Blutstrom als nach IAsp 0,2 E/kg und eine um den Faktor 2 gegenüber IAsp erhöhte Insulinexposition während der ersten 30 Minuten. Dies führte gemäß euglykämischen Glucose-Clamp-Daten aus drei dieser Studien zu einem um 4,9 Minuten früheren Wirkbeginn der glukosesenkenden Wirkung (p < 0,001) sowie zu einer um 74 % höheren glukosesenkenden Wirkung innerhalb der ersten 30 Minuten (p < 0,001). Dementsprechend waren in einer weiteren explorativen Studie nach subkutaner Injektion von Faster-acting Insulin aspart der postprandiale Glukoseanstieg um durchschnittlich 1,24 mmol/l (22,3 mg/dl) (Messung eine Stunde nach einer standardisierten Mahlzeit) und die Plasmaglukosekonzentrationen in den ersten 2 Stunden um durchschnittlich 26 % gegenüber IAsp reduziert. In einer pharmakologischen Studie zur kontinuierlichen subkutanen Insulininjektion (CSII) waren nach Faster-acting Insulin aspart die Insulinexposition während der ersten 30 Minuten um den Faktor 3 und die glukosesenkende Wirkung nach Injektion von Faster-acting Insulin aspart um ca. 100 % gegenüber IAsp erhöht. Die Verträglichkeit von Faster-acting Insulin aspart ist nach den vorläufigen Daten vergleichbar zu IAsp, ebenso die Kompatibilität in der Pumpenanwendung. In der Zusammenfassung zeigen die pharmakologischen Studien zu Faster-acting Insulin aspart im Vergleich zu IAsp ein doppelt so schnelles initiales Auftreten von Insulin im Blut, eine 2-fach (subkutane Injektion) bzw. 3-fach (CSII) so hohe Insulinexposition innerhalb der ersten 30 Minuten und eine um 74 % (subkutane Injektion) bzw. ca. 100 % (CSII) höhere glukosesenkende Wirkung in diesem Zeitraum. Daten aus zwei Phase-IIIa-Studien bestätigen die mit Faster-acting Insulin aspart erzielbare Reduktion von postprandialen Blutzuckeranstiegen im Vergleich zu IAsp.

Abstract

Faster-acting Insulin aspart is a formulation based on insulin aspart (IAsp), further developed by adding the excipients niacinamide and L-arginine, which are considered to be safe. The pooled analysis of six pharmacological studies with a randomised cross-over design in adult people with type 1 diabetes resulted in a approximately 5 minutes earlier onset of appearance of insulin in the bloodstream for the subcutaneous injection of Faster-acting Insulin aspart 0.2 U/kg compared with IAsp 0.2 U/kg and a 2-fold increased insulin exposure in the first 30 minutes versus IAsp. According to euglycaemic glucose clamp data from three out of these studies, this led to a 4.9 minutes earlier onset of the glucose-lowering action (p < 0.001) as well as a 74 % higher glucose lowering effect within the first 30 minutes (p < 0.001). This is consistent with the results of another exploratory study, which demonstrated a mean reduction of postprandial glucose excursion by 1.24 mmol/l (22.3 mg/dl) after subcutaneous (s. c.) injection of Faster-acting Insulin aspart (measured one hour after a standardised meal) and of the plasma glucose concentration in the first two hours by 26 % versus IAsp. In a pharmacological study on continuous subcutaneous insulin injection (CSII), there was a 3-fold increased insulin exposure in the first 30 minutes and the glucose lowering effect was increased by approximately 100 % in the first 30 minutes after injection of Faster-acting Insulin aspart compared with IAsp. According to preliminary data, the tolerability of Faster-acting Insulin aspart is similar to that of IAsp, the same holds true for compatibility in pump use. In summary, the pharmacological trials on Faster-acting Insulin aspart demonstrate a twice as fast occurrence of insulin in the blood compared with IAsp, a 2-fold (s. c. administration) and 3-fold (CSII) increased insulin exposure within the first 30 minutes and a 74 % (s. c. administration) and about 100 % (CSII) higher glucose lowering effect in this period of time. Data from two phase IIIa studies confirm the reduction of postprandial glucose excursions that can be achieved with Faster-acting Insulin aspart compared with IAsp.

Schlüsselwörter

Diabetes - Insulin - Pharmakokinetik - Pharmakodynamik - Faster-acting Insulin aspart - CSII

Key words

diabetes - insulin - pharmacokinetic - pharmacodynamics - faster-acting insulin aspart - CSII

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