Better glycaemic control with once-weekly insulin icodec versus once-daily insulin degludec in adults with insulin-naive type 2 diabetes (ONWARDS 3)

Background and aims: Efficacy and safety of once-weekly insulin icodec (icodec) versus once-daily insulin degludec (degludec) in adults with insulin-naïve type 2 diabetes were examined in ONWARDS 3, a 26-week, randomised, double-blind, double-dummy, treat-to-target, phase 3a trial.Materials and methods: Participants (n=588) were randomised 1:1 to icodec or degludec. Key outcomes are shown in the table. Theprimary endpoint was HbA 1c change from baseline to week 26.Results: Estimated mean HbA1c change from baseline was greater with icodec (−1.57%; baseline: 8.55%) versus degludec (−1.36%; baseline: 8.48%); estimated treatment difference: −0.21%-points (95% CI −0.34, −0.08), confirming non-inferiority (p<0.0001) and superiority (p=0.0016). Level 2 or 3 hypoglycaemia rates were numerically but not statistically significantly higher with icodec versus degludec in the on-treatment period (table). Odds of achieving HbA 1c <7% without level 2 or 3 hypoglycaemia were statistically significantly higher with icodec versus degludec. There were no significant differences in weekly insulin dose from week 24 to 26 or body weight change from baseline to week 26 between arms. No unexpected safety findings were observed.Conclusion: Overall, once-weekly icodec demonstrated superior HbA1c reduction versus once-daily degludec with low level 2 or 3 hypoglycaemia rates in both arms. Icodec may facilitate insulin treatment acceptance and adherence by reducing basal insulin injections from ≥365 to 52 per year.