Comparable Total Exposure of Once-Weekly Insulin Icodec between Different Subcutaneous Injection Regions

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. 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) . 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) . In conclusion, insulin icodec can be administered s.c. in the thigh, abdomen or upper arm with essentially similar exposure and glucose-lowering effect. Disclosure L. Plum-moerschel: Other Relationship; Eli Lilly and Company, Gan & Lee Pharmaceuticals, Novo Nordisk A/S. L. R. Andersen: None. S. Hansen: None. U. Hövelmann: None. P. Krawietz: None. N. R. Kristensen: Employee; Novo Nordisk. L. Lang lehrskov: Employee; Novo Nordisk A/S. H. Haahr: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. Funding Novo Nordisk