ONWARDS 10: Switching to Weekly Insulin Icodec Without A Loading Dose

Key Takeaways

• Once-weekly icodec without an initial additional dose was associated with non-inferior HbA1c change versus daily glargine U100 at 26 weeks.
• Greater time in range was reported with icodec, and self-measured blood glucose did not rise after initiation.
• Clinically significant or severe hypoglycaemia was numerically lower with icodec, and investigators concluded that omitting the additional first dose simplified switching without compromising initial glycaemic control.

In ONWARDS 10, adults with basal-insulin-treated type 2 diabetes who switched to once-weekly icodec without an extra first dose had an estimated treatment difference of -0.2 percentage points for HbA1c change from baseline to week 26 versus once-daily glargine U100. Within the trial’s non-inferiority framework, glycaemic control was maintained with this simplified switch protocol. The trial asked whether the switch protocol could omit a one-time additional first dose.

ONWARDS 10 was a 26-week, open-label, phase 3b, treat-to-target randomized trial in adults with basal-insulin-treated type 2 diabetes and HbA1c 7.0%-10.0%. Overall, 412 participants were randomized 1:1, with 206 assigned to each arm: once-weekly insulin icodec without a one-time additional first dose or once-daily glargine U100. Baseline HbA1c was 8.1% in the icodec group and 8.0% in the glargine group. The primary endpoint was change in HbA1c from baseline to week 26, tested against a 0.3 percentage-point non-inferiority margin.

At week 26, estimated mean HbA1c was 7.2% with icodec and 7.5% with glargine U100. The estimated treatment difference for HbA1c change was -0.2 percentage points. The 95% confidence interval ranged from -0.4 to -0.1, and p < 0.0001 confirmed non-inferiority. These findings supported non-inferiority for HbA1c change with the simplified switch protocol.

Time in range also favored icodec. Estimated mean change from baseline to weeks 22-26 was 18.0 percentage points with icodec and 12.1 percentage points with glargine U100. The estimated treatment difference was 5.9 percentage points, with a 95% confidence interval of 2.6 to 9.2 and p = 0.0005. Self-measured blood glucose also did not increase after icodec initiation during the early switch period.

The combined clinically significant or severe hypoglycaemia rate was numerically lower with icodec than with glargine U100, at 0.45 versus 0.59 episodes per patient-year of exposure. Investigators concluded that omitting the one-time additional dose simplified switching to icodec without compromising initial glycaemic control during the 26-week trial.