Icodec had to be taken subcutaneously once weekly on the same day each week, while IGlar U100 had to be taken subcutaneously once daily at any time of the day but at the same time every day. Participants in the icodec LD group received an initial 100% loading dose with the first dose of icodec (i.e., the first weekly dose was doubled), and then it was reverted to the calculated weekly dose at week 2 ( Supplementary Fig. For those who had been receiving twice-daily basal insulin or once-daily IGlar U300 at baseline, starting doses of IGlar U100 were decreased by 20% to minimize the postswitch hypoglycemia risk for the icodec LD and NLD groups, the dose was similarly decreased by 20% and then multiplied by 7 to derive the once-weekly dose. Participants who had been receiving once-daily basal insulin (except for those receiving IGlar U300) at baseline underwent a “unit to unit” switch to icodec (700 units/mL prefilled pen injector) (Novo Nordisk, Bagsvaerd, Denmark) or IGlar U100 (100 units/mL) (SoloSTAR prefilled pen injector Sanofi, Paris, France) based on their daily dose to derive the equivalent once-weekly dose for the icodec LD and NLD groups, the daily dose was multiplied by 7. The initial dose of the trial products was based on the pretrial insulin daily doses. Native Hawaiian or other Pacific Islander In a phase 2 trial in insulin-naive individuals with type 2 diabetes, once-weekly icodec resulted in a similar glucose-lowering effect and safety profile compared with once-daily insulin glargine 100 units/mL (IGlar U100) ( 14).
At steady state, a slow, continuous release of icodec from the inactive albumin-bound depot provides effective glucose lowering throughout the week ( 13), which was shown to be near evenly distributed across a 1-week dosing interval ( 12). With each weekly injection, the pool of albumin-bound icodec gradually increases, until steady state is reached after 3–4 weeks when the full glucose-lowering effect is achieved and insulin clearance matches administered insulin dose.
After subcutaneous injection and absorption into the circulation, icodec monomers bind to albumin to form an essentially inactive depot, from which icodec molecules slowly reach insulin receptors at target tissues to stimulate glucose lowering. The long half-life of icodec can be attributed to its strong, reversible albumin binding, reduced enzymatic degradation, and slow receptor-mediated clearance ( 13). It has stable pharmacokinetic and pharmacodynamic profiles, with a half-life of ∼1 week, supporting once-weekly administration ( 12). Insulin icodec (icodec) is a novel basal insulin analog for subcutaneous administration for the treatment of diabetes.
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