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

Abstract

BackgroundManagement 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.ObjectiveThe 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.MethodsThis 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 (AUCIDeg,τ,SS) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (Cmax,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 (AUCGIR,τ,SS), and the maximum GIR at steady state (GIRmax,IDeg,SS).ResultsTotal exposure (AUCIDeg,τ,SS) and maximum concentration (Cmax,IDeg,SS) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUCIDeg,τ,SS and Cmax,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 AUCIDeg,0–12h,SS/AUCIDeg,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 AUCGIR,τ,SS (the primary endpoint of this study) and GIRmax,IDeg,SS. Estimated mean age group ratios (elderly/younger adult) for AUCGIR,τ,SS and GIRmax,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. ConclusionsThe 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 su...

A Comparison of Pharmacokinetic and Pharmacodynamic Properties Between Faster-Acting Insulin Aspart and Insulin Aspart in Elderly Subjects with Type 1 Diabetes Mellitus

“…Accordingly, to our knowledge, glucose clamp studies comparing the pharmacokinetic and pharmacodynamic properties of an insulin between elderly and younger adults and/or between two insulins in elderly subjects have only been conducted for a few insulin products [19, 20, 28]. Therefore, a strength of the current study was the use of the euglycaemic glucose clamp technique to assess the pharmacodynamic properties.…”

Clinical use of insulin degludec

“…Importantly, the ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in patients with T1DM and T2DM are maintained in various subpopulations, such as the elderly and those with hepatic or renal impairment (including those with end-stage renal disease) [30][31][32]. The pharmacokinetic and pharmacodynamic properties of IDeg are maintained in both of its formulations, U100 and U200 [33].…”

“…IDeg is licensed for use in elderly patients (65 years of age) and is also suitable for use in patients with renal or hepatic impairment [34] as supported by clinical evidence, indicating that the pharmacokinetic characteristics of IDeg are preserved in these patient populations [30][31][32]. However, as recommended for other basal insulins [16,17], glucose-monitoring should be performed more frequently in these specific patient populations [34].…”

Insulin U100, 200, 300 or 500?

“…[12][13][14] There was no clinically relevant difference REVIEW in the handling of insulin degludec by younger people compared with an older group. 15 The duration of action of insulin degludec was reported to be >42 h. 11 …”