Abstract 157: Comparable total exposure of once-weekly insulin icodec between different subcutaneous injection regions

Background: People with diabetes may inject s.c. insulin in different body regions. To address if choice of injection region affects insulin icodec exposure and glucose-lowering effect, this study compared icodec administration in different s.c. injection regions. Methods: In a randomized, open-label, three-period crossover trial, 25 individuals with T2D on basal insulin (22 males; mean ± SD age 60 ± 7 yrs, BMI 30.7 ± 4.6 kg/m2) received single s.c. icodec doses (5.6 U/kg) in the thigh, abdomen and upper arm (9-13 weeks washout). Blood was sampled for pharmacokinetics (PK) until 840 h (35 days) post-dose. Glucose-lowering effect was assessed at 36-60 h post-dose in an automated glucose clamp (target 135 mg/dL). Results: Total icodec exposure (AUC0-∞,SD) was similar after single-dose s.c. injection in the thigh, abdomen and upper arm [Table]. Maximum concentration (Cmax,SD) was higher for abdomen/upper arm vs. thigh. Extrapolation of PK profiles to steady state using a PK model showed smaller differences in Cmax,SS for abdomen/upper arm vs. thigh than after single dose. Partial glucose-lowering effect 36-60 h after single dose (AUCGIR,36-60h,SD) was comparable across injection regions (geom. mean [CV%] of 1961 [51], 2130 [52] and 2391 [40] mg/kg for thigh, abdomen and upper arm). Conclusion: Insulin icodec can be administered s.c. in the thigh, abdomen or upper arm withessentially similar exposure and glucose-lowering effect.