Simplified Switching to Once‐Weekly Insulin Icodec Without an Initial One‐Time Additional Dose Versus Once‐Daily Insulin Glargine U100 in Basal Insulin‐Treated Type 2 Diabetes ( ONWARDS 10): A Randomised Controlled Trial

ABSTRACT Aims ONWARDS 10 assessed switching from daily basal insulins to once‐weekly insulin icodec without a one‐time additional dose at first injection. Materials and Methods In this treat‐to‐target, open‐label, 26‐week, phase 3b trial, adults with basal‐insulin‐treated type 2 diabetes (T2D) with glycated haemoglobin [HbA 1c ] 7.0%–10.0% were randomised to once‐weekly icodec without an initial one‐time additional dose or to once‐daily insulin glargine U100. Primary endpoint was change in HbA 1c from baseline to week 26 (non‐inferiority margin: 0.3%‐points); secondary endpoints included change in time in range (TIR; 70–180 mg/dL [3.9–10.0 mmol/L]) from baseline (weeks −4 to 0) to weeks 22–26, and number of combined clinically significant or severe hypoglycaemic episodes (weeks 0–31). Results Overall, 412 participants were randomised to icodec ( n = 206) or glargine U100 ( n = 206). At week 26, estimated mean HbA 1c was 7.2% with icodec (baseline 8.1%) and 7.5% with glargine U100 (baseline 8.0%). Estimated treatment difference (ETD) for change in HbA 1c was −0.2%‐points (95% confidence interval [CI]: −0.4, −0.1), confirming non‐inferiority of icodec versus glargine U100 ( p < 0.0001). Self‐measured blood glucose did not increase following icodec initiation. Change in TIR from baseline to weeks 22–26 was statistically significantly higher with icodec than with glargine U100 (estimated mean change: 18.0%‐points vs. 12.1%‐points; ETD: 5.9%‐points [95% CI: 2.6, 9.2], p = 0.0005). Combined clinically significant or severe hypoglycaemia rate was numerically lower with icodec than with glargine U100 (0.45 vs. 0.59 episodes per patient‐year of exposure). Conclusions Omitting the one‐time additional dose simplifies switching to icodec in adults with basal‐insulin‐treated T2D without compromising initial glycaemic control. Trial Registration: ClinicalTrials.gov identifier: NCT06340854