Details

Autor(en) / Beteiligte

• Plum-Mörschel, Leona
• Andersen, Lizette Ravn
• Hansen, Solvejg
• Hövelmann, Ulrike
• Krawietz, Patricia
• Kristensen, Niels Rode
• Lehrskov, Lars Lang
• Haahr, Hanne

Titel

Pharmacokinetic and Pharmacodynamic Characteristics of Insulin Icodec After Subcutaneous Administration in the Thigh, Abdomen or Upper Arm in Individuals with Type 2 Diabetes Mellitus

Ist Teil von

• Clinical drug investigation, 2023-02, Vol.43 (2), p.119-127

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. ClinicalTrials.gov Identifier NCT04582448.