Novo Nordisk announced headline results from the ONWARDS 3 and ONWARDS 4 phase 3a trials with once-weekly insulin icodec in adults with type 2 diabetes. ONWARDS 3 (insulin-naïve people with type 2 diabetes) ONWARDS 3 is a phase 3a, double-blind 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin degludec. Both are in combination with non-insulin anti-diabetic treatment in 588 people with type 2 diabetes who have not previously been treated with insulin.

The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared with insulin degludec. From an overall baseline HbA1c of 8.5%, once-weekly insulin icodec achieved a superior reduction in estimated HbA1c of –1.57% compared with –1.36% for insulin degludec (estimated treatment difference: –0.21%). In the trial, there was no statistically significant difference in estimated rates of severe or clinically significant hypoglycaemia (blood glucose below 3 mmol/L) with 0.31 events per patient-year exposed to once-weekly insulin icodec and 0.15 events per patient-year exposed to insulin degludec.

In the trial, once-weekly insulin icodec appeared to have a safe and well-tolerated profile. ONWARDS 4 (basal-bolus treatment in people with type 2 diabetes) ONWARDS 4 is a phase 3a, 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin glargine U100, both in combination with mealtime insulin (insulin aspart administered two to four times daily), in 582 people with type 2 diabetes. The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 26 with insulin icodec compared with insulin glargine.

From an overall baseline HbA1c of 8.3% once-weekly insulin icodec achieved a reduction in estimated HbA1c of –1.16% compared with –1.18% for insulin glargine (estimated treatment difference: 0.02%). In the trial, there was no statistically significant difference in estimated rates of severe or clinically significant hypoglycaemia (blood glucose below 3 mmol/L) with 5.64 events per patient-year exposed to once-weekly insulin icodec and 5.62 events per patient-year exposed to insulin glargine. In the trial, once-weekly insulin icodec appeared to have a safe and well-tolerated profile.