Pharmacokinetic/Pharmacodynamic Modeling of Efficacy and Hypoglycemia Rate When Switching From Once-Daily Basal Insulin to Once-Weekly Insulin Icodec Without or With a One-Time Additional Dose in Insulin-Experienced Individuals With Type 2 Diabetes

OBJECTIVE: Insulin icodec (icodec), a once-weekly basal insulin analog, has been investigated in the phase 3a ONWARDS clinical trial program. This pharmacokinetic (PK)/pharmacodynamic (PD) modeling analysis of data from the ONWARDS 2 and 4 trials investigated efficacy outcomes and hypoglycemia rate in insulin-experienced individuals with type 2 diabetes when switching from daily basal insulin to icodec without or with a 50% one-time additional dose for the first injection only. METHODS: Data from 2 randomized, 26-week, phase 3a trials of insulin-experienced individuals with type 2 diabetes on a basal (ONWARDS 2) or basal-bolus (ONWARDS 4) insulin regimen were used for PK/PD model development and validation. The effect of switching to icodec without versus with a 50% one-time additional dose on prebreakfast self-measured blood glucose, glycated hemoglobin, weekly insulin dose, and clinically significant hypoglycemia was assessed. RESULTS: Model predictions suggested that switching to icodec without versus with a 50% one-time additional dose would result in a mild, transient (1-2 weeks) increase in prebreakfast self-measured blood glucose after treatment initiation that would decrease to matching levels between groups by week 4 and remain similar between groups until end of treatment (week 26). There were no model-predicted differences between groups in glycated hemoglobin reduction or clinically significant hypoglycemia over the 26-week study period or in weekly icodec dose at week 26. CONCLUSIONS: This PK/PD model analysis suggests that omitting administration of a 50% one-time additional dose when switching to icodec from daily basal insulin would not be predicted to result in any sustained effects.