Simplified Switching to Once-Weekly Insulin Icodec Without an Initial One-Time Additional Dose Versus Once-Daily...

ONWARDS 10 assessed switching from daily basal insulins to once-weekly insulin icodec without a one-time additional dose at first injection.

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).

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).

Omitting the one-time additional dose simplifies switching to icodec in adults with basal-insulin-treated T2D without compromising initial glycaemic control.

ClinicalTrials.gov identifier: NCT06340854.