Insulin icodec* is a novel basal insulin analog designed for single once-weekly (OW) subcutaneous injection. This randomized, double–blind, double–dummy trial investigated the pharmacokinetics (PK), pharmacodynamics (PD) and safety of insulin icodec. Fifty individuals with type 2 diabetes (insulin treated±metformin; 43 men; mean±SD age 57±5 years, BMI 30.1±2.7 kg/m2, A1C 7.4±0.6%) received OW insulin icodec (12, 20 or 24 nmol/kg) plus once–daily (OD) placebo (N=13, 13, 12) or OD insulin degludec (0.4 U/kg) plus OW placebo (N=12) for 5 weeks in 3 dose level cohorts. PD properties were investigated at close to steady state in 24-h glucose clamps on days 2 and 7 after the last insulin icodec dose. Median tmax,insulin icodec was 16 h and geometric mean t½,insulin icodec was 196 h with no systematic differences between dose levels. The glucose–lowering effect over a weekly dosing interval was derived from the observed PK/PD data using a PK/PD model and showed close to even distribution over the 7 days across all dose levels (Figure). The adverse event (AE) incidence did not increase with increasing insulin icodec dose (100%, 69%, 75%, respectively). There were no serious or severe AEs, severe hypoglycemic episodes or injection site reactions.
In conclusion, insulin icodec was safe and well-tolerated and showed PK/PD properties supporting once-weekly administration at clinically relevant dose levels. * Proposed INN.
U. Hövelmann: None. L. Brøndsted: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. N.R. Kristensen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. R. Ribel-Madsen: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. J. DeVries: Advisory Panel; Self; Novo Nordisk A/S, Zealand Pharma A/S. Consultant; Self; Metronom Health. Employee; Self; Profil Institute for Clinical Research. T. Heise: Advisory Panel; Self; Mylan, Novo Nordisk A/S. Research Support; Self; ADOCIA, Aerami, Becton, Dickinson and Company, Biocon, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Gan & Lee Pharmaceuticals, MedImmune, Merck KGaA, Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Sanofi, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Eli Lilly and Company, Novo Nordisk A/S. H. Haahr: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S.