The Distinct Prandial and Basal Pharmacodynamics of IDegAsp Observed in Younger Adults Are Preserved in Elderly Subjects with Type 1 Diabetes

Martina Brunner, Thomas Pieber, Stefan Korsatko, Harald Kojzar, Anne Louise Svendsen, Hanne Haahr, Martina Brunner, Thomas Pieber, Stefan Korsatko, Harald Kojzar, Anne Louise Svendsen, Hanne Haahr

Abstract

Background: Management of diabetes in elderly patients is complicated by the elevated risk of insulin-induced hypoglycaemia. This is the first study to report the pharmacodynamic and pharmacokinetic characteristics of IDegAsp (insulin degludec [IDeg]/insulin aspart [IAsp]), a soluble co-formulation of a long-acting basal insulin analogue (IDeg) and a rapid-acting insulin analogue (IAsp) in a single injection, in elderly and younger adult subjects with type 1 diabetes using a glucose clamp.

Methods: In this randomised, single-centre, double-blind, single-dose (SD), two-period, crossover trial, 15 elderly subjects (aged ≥ 65 years) and 13 younger adults (aged 18-35 years) with type 1 diabetes were randomly assigned to two SD administrations of 0.5 U/kg IDegAsp or biphasic insulin aspart 30 (control) followed by a 26-h euglycaemic glucose clamp and 120-h pharmacokinetic blood sampling. The glucose infusion rate (GIR) profiles were extrapolated to simulated steady-state (SS) conditions using pharmacodynamic models.

Results: IDegAsp GIR profiles showed a distinct peak and rapid onset of action from IAsp followed by a separate and flat basal action from IDeg. Mean 24-h area under the GIR curve was similar in elderly subjects vs. younger adults (mean ratio 1.01 [95% confidence interval 0.69-1.47]). Simulated SS pharmacodynamic profiles with once-daily IDegAsp showed a parallel upshift in GIR profiles vs. SD profiles. The shape of the IDegAsp pharmacodynamic profile was retained with twice-daily dosing under simulated SS conditions. IDegAsp was well tolerated.

Conclusions: The distinct prandial and basal pharmacodynamics of IDegAsp observed in younger adults were preserved in elderly subjects with type 1 diabetes. The glucose-lowering effect of IDegAsp was similar in elderly subjects and younger adults with type 1 diabetes.

Trial registration: ClinicalTrials.gov NCT01174303.

Figures

Fig. 1
Fig. 1
a Mean glucose infusion rate profiles following a single dose (0.5 U/kg) of insulin degludec/insulin aspart in subjects of two different age groups with type 1 diabetes. b Simulated mean glucose infusion rate profiles of insulin degludec/insulin aspart (0.5 U/kg) at steady state in elderly and younger adult subjects with type 1 diabetes
Fig. 2
Fig. 2
a Mean glucose infusion rate profile following a single dose (0.5 U/kg) of insulin degludec/insulin aspart (IDegAsp) or biphasic insulin apart 30 (BIAsp 30) in elderly subjects with type 1 diabetes. b Raw mean glucose infusion rate profile
Fig. 3
Fig. 3
Simulated mean glucose infusion rate profiles of insulin degludec/insulin aspart administered twice daily (0.25 U/kg per dose) at steady state in elderly and younger adult subjects with type 1 diabetes

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Source: PubMed

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