Pharmacokinetic and Pharmacodynamic Characteristics of Insulin Icodec After Subcutaneous Administration in the Thigh, Abdomen or Upper Arm in Individuals with Type 2 Diabetes Mellitus
Clinical drug investigation(2023)
摘要
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.
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关键词
insulin icodec,subcutaneous administration,diabetes mellitus,pharmacokinetic
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