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Background and Objective: Individuals with diabetes mellitus may prefer different body regions for subcutaneous insulin administration. This trial investigated whether choice of injection region affects exposure and glucose-lowering effect of once-weekly basal insulin icodec., Methods: In a randomised, open-label, crossover trial, 25 individuals with type 2 diabetes received single subcutaneous icodec injections (5.6 U/kg) in the thigh, abdomen or upper arm (9-13 weeks' washout). Pharmacokinetic blood sampling occurred frequently until 35 days post-dose. Partial glucose-lowering effect was assessed 36-60 h post-dose in a glucose clamp (target 7.5 mmol/L). Steady-state pharmacokinetics following multiple once-weekly dosing were simulated using a two-compartment pharmacokinetic model., Results: Total icodec exposure (area under the curve from zero to infinity after single dose; AUC 0-∞,SD ) was similar between injection in the thigh, abdomen and upper arm (estimated AUC 0-∞,SD ratios [95% confidence interval]: abdomen/thigh 1.02 [0.96-1.09], p = 0.473; upper arm/thigh 1.04 [0.98-1.10], p = 0.162; abdomen/upper arm 0.98 [0.93-1.05], p = 0.610). Maximum icodec concentration (C max ) after single dose was higher for abdomen (by 17%, p = 0.002) and upper arm (by 24%, p < 0.001) versus thigh. When simulated to steady state, smaller differences in C max were seen for abdomen (by 11%, p = 0.004) and upper arm (by 16%, p < 0.001) versus thigh. Geometric mean [coefficient of variation] glucose-lowering effect 36-60 h post-dose was comparable between the thigh (1961 mg/kg [51%]), abdomen (2130 mg/kg [52%]) and upper arm (2391 mg/kg [40%])., Conclusion: Icodec can be administered subcutaneously in the thigh, abdomen or upper arm with no clinically relevant difference in exposure and with a similar glucose-lowering effect., Gov Identifier: NCT04582448., (© 2023. The Author(s).)

Background: Fast-acting insulin aspart (faster aspart) is insulin aspart set in a new formulation with faster initial absorption after subcutaneous administration. This study investigated the pharmacokinetic properties, including the absolute bioavailability, of faster aspart when administered subcutaneously in the abdomen, upper arm or thigh., Methods: In a randomised, open-label, crossover trial, 21 healthy male subjects received a single injection of faster aspart at five dosing visits: 0.2 U/kg subcutaneously in the abdomen, upper arm and thigh, intramuscularly in the thigh and 0.02 U/kg intravenously. Blood sampling for pharmacokinetics was performed pre-dose and frequently thereafter until 12 h post-dose (8 h after intravenous administration)., Results: Onset of appearance (~3 min), time to 50% of maximum concentration (t Early 50% Cmax ; ~20 min) and time to maximum concentration (t max ; ~55 min) were all similar between injection regions. Early exposure within the first 2 h after injection (AUC IAsp,0-1h and AUC IAsp,0-2h ) as well as maximum concentration (C max ) were comparable for the abdomen and upper arm, but were ~25% lower for the thigh as seen previously for other mealtime insulin products. Total exposure (AUC IAsp,0-t ) was similar for the abdomen, upper arm and thigh, and absolute bioavailability was ~80% after subcutaneous administration of faster aspart in all three injection regions., Conclusion: The current study supports the ultra-fast pharmacokinetic characteristics of faster aspart across different injection regions, with administration in the abdomen and upper arm resulting in greater early exposure than in the thigh. ClinicalTrials.gov identifier: NCT02089451.

Background: Due to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption. This study investigated the pharmacological properties of faster aspart in elderly subjects with type 1 diabetes mellitus (T1DM)., Methods: In a randomised, double-blind, two-period crossover trial, 30 elderly (≥65 years) and 37 younger adults (18-35 years) with T1DM received single subcutaneous faster aspart or IAsp dosing (0.2 U/kg) and underwent an euglycaemic clamp (target 5.5 mmol/L) for up to 12 h., Results: The pharmacokinetic and pharmacodynamic time profiles were left-shifted for faster aspart versus IAsp. In each age group, onset of appearance occurred approximately twice as fast (~3 min earlier) and early exposure (area under the concentration-time curve [AUC] for serum IAsp from time zero to 30 min [AUC IAsp,0-30 min ]) was greater (by 86% in elderly and 67% in younger adults) for faster aspart than for IAsp. Likewise, onset of action occurred 10 min faster in the elderly and 9 min faster in younger adults, and early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 30 min [AUC GIR,0-30 min ]) was greater (by 109%) for faster aspart than for IAsp in both age groups. Total exposure (AUC IAsp,0-t ) and the maximum concentration (C max ) for faster aspart were greater (by 30 and 28%, respectively) in elderly than in younger adults. No age group differences were seen for the total (AUC GIR,0-t ) or maximum (GIR max ) glucose-lowering effect., Conclusion: This study demonstrated that the ultra-fast pharmacological properties of faster aspart are similar in elderly subjects and younger adults with T1DM. ClinicalTrials.gov Identifier: NCT02003677., Competing Interests: Compliance with Ethical StandardsAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.FundingThis study was funded by Novo Nordisk.Conflict of interestTim Heise is a shareholder of Profil, which has received research funds from Adocia, AstraZeneca, Becton Dickinson, Biocon, Boehringer Ingelheim, Dance Biopharm, Eli Lilly, Grünenthal, Gulf Pharmaceutical Industries, Johnson & Johnson, Marvel, MedImmune, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, Sanofi, Senseonics and Zealand Pharma. In addition, Tim Heise is a member of advisory panels for Novo Nordisk and received speaker honoraria and travel grants from Eli Lilly, Mylan and Novo Nordisk. Kirstine Stender-Petersen, Jacob Bonde Jacobsen and Hanne Haahr are employees and shareholders of Novo Nordisk. Eric Zijlstra received travel grants from Dance Biopharm and Novo Nordisk and speaker honoraria from Novo Nordisk and Roche Diabetes Care. Ulrike Hövelmann declares no conflicts of interest.