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Background and Objectives: Patients with diabetes mellitus inject insulin in different regions of the body. This study investigated the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a new-generation once-daily basal insulin with an ultra-long duration of action, after subcutaneous (SC) administration in different injection regions. Methods: In this study, 20 healthy subjects received single SC doses of IDeg (0.4 U/kg; separated by 13-21 days) in the thigh, abdomen and deltoid in a randomised, open-label, single-centre, single-dose, complete crossover trial. Each dose was followed by a 24-h euglycaemic clamp and 120-h pharmacokinetic blood sampling. The obtained pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by simulation using a pharmacokinetic/pharmacodynamic model. Results: Total IDeg exposure [area under the IDeg serum concentration-time curve 0-120 h after a single dose (AUC)] and maximum serum concentration [maximum IDeg serum concentration after a single dose ( C)] were higher (6-7 and 23-27 %, respectively) following a single SC dose in the deltoid or abdomen, compared with the thigh, as also observed with other insulin preparations. No statistical difference was observed in these measures between deltoid and abdominal administration. No pronounced differences were observed in the glucose-lowering effect of IDeg [area under the glucose infusion rate (GIR) curve 0-24 h after a single dose (AUC) and maximum GIR after a single dose (GIR)] when injected in the thigh, abdomen or deltoid (AUC 2,572, 2,833 and 2,960 mg/kg, respectively). Simulated mean steady-state pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg exposure and effect regardless of injection region, with comparable total glucose-lowering effects [area under the GIR curve at steady state (AUC)] between the thigh, abdomen and deltoid. Conclusions: These findings support administering IDeg SC in the thigh, upper arm or abdominal wall without affecting IDeg absorption or effect at steady state. [ABSTRACT FROM AUTHOR]

Background and Objective: Insulin degludec is a basal insulin with a slow and distinct absorption mechanism resulting in an ultra-long, flat, and stable pharmacokinetic profile in patients with diabetes mellitus. The aim of this study was to examine the effect of hepatic impairment on the single-dose pharmacokinetics of insulin degludec. Methods: Twenty-four subjects, allocated to one of four groups ( n = 6 per group) based on level of hepatic impairment (normal hepatic function, Child-Pugh grade A, B, or C), were administered a single subcutaneous dose of 0.4 U/kg insulin degludec. Blood samples up to 120 h post-dose and fractionated urine samples were collected to measure pharmacokinetic parameters. Results: No difference was observed in pharmacokinetic parameters [area under the 120-h serum insulin degludec concentration-time curve (AUC), maximum insulin degludec concentration ( C), and apparent clearance (CL/ F)] for subjects with impaired versus normal hepatic function after a single dose of insulin degludec. The geometric mean [coefficient of variation (CV) %] AUC values were 89,092 (16), 83,327 (15), 88,944 (23), and 79,846 (19) pmol·h/L for normal hepatic function and mild, moderate, and severe hepatic impairment, respectively. Simulated steady-state insulin degludec pharmacokinetic profiles showed an even distribution of exposure across a 24-h dosing interval regardless of hepatic function status. Conclusions: The ultra-long pharmacokinetic properties of insulin degludec were preserved in subjects with hepatic impairment and there were no statistically significant differences in absorption or clearance compared with subjects with normal hepatic function. [ABSTRACT FROM AUTHOR]