Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus

Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia.

The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults.

This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18–35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC_IDeg,τ,SS) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C_max,IDeg,SS). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC_GIR,τ,SS), and the maximum GIR at steady state (GIR_max,IDeg,SS).

Total exposure (AUC_IDeg,τ,SS) and maximum concentration (C_max,IDeg,SS) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC_IDeg,τ,SS and C_max,IDeg,SS and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively. Mean AUC_{IDeg,0–12h,SS}/AUC_IDeg,τ,SS was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC_GIR,τ,SS (the primary endpoint of this study) and GIR_max,IDeg,SS. Estimated mean age group ratios (elderly/younger adult) for AUC_GIR,τ,SS and GIR_max,IDeg,SS and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47–1.31) and 0.80 (95 % CI 0.54–1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects.

The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes.

Clinical trials.gov number: NCT00964418