Once-Weekly Insulin Icodec vs Once-Daily Insulin Glargine U100 in Combination with Bolus Insulin in Individuals with Type 2 Diabetes on Basal-Bolus Regimens (ONWARDS 4)

Objective ONWARDS 4 was a 26-week, randomised, treat-to-target, phase 3 trial, designed to assess efficacy and safety of once-weekly insulin icodec (icodec) vs once-daily insulin glargine U100 (glargine) in a basal-bolus insulin regimen in type 2 diabetes(T2D). Method Adults (n=582) with T2D (HbA1c 7.0–10.0%) on a basal-bolus regimen were randomised 1:1 to icodec or glargine, both in combination with multiple daily injections of insulin aspart. Primary endpoint was change in HbA1c from baseline to week 26(non-inferiority margin 0.3%). Result At week 26, from a mean baseline of 8.3%, estimated HbA1c reductions were -1.16% (icodec) and -1.18% (glargine), confirming non-inferiority for icodec vs glargine (estimated treatment difference [ETD]: 0.02% [95% CI, -0.11 to 0.15]; p<0.0001). Overall rates of combined level 2 or level 3 hypoglycaemia were comparable between treatments (5.64 [icodec] and 5.62 [glargine] per patient year of exposure; estimated rate ratio: 0.99 [95% CI, 0.73 to 1.33]; p=0.929). Mean total weekly basal component of the total insulin dose from week 24–26 was significantly higher in the icodec arm vs the glargine arm (305 U/week vs 279 U/week; p=0.0286), while the mean total weekly bolus insulin component was significantly lower (197 U/week vs 255 U/week; p<0.0001). Estimated mean body weight change was 2.73 kg(icodec) and 2.16 kg (glargine) (ETD: 0.57 kg [95% CI, -0.39 to 1.54]; p=0.2444). Conclusion Once-weekly icodec demonstrated comparable improvements in glycaemic control with fewer basal insulin injections, with a comparable hypoglycaemia profile vs once-daily glargine in individuals with T2D on a basal-bolus regimen. Publication History Article published online: 02 May 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany