Novo Nordisk announced headline results from the ONWARDS 5 phase 3a trial with once-weekly insulin icodec in people with type 2 diabetes. The ONWARDS 5 trial was a 52-week, open-label efficacy and safety treat-to-target trial investigating once-weekly insulin versus once-daily basal insulin (insulin degludec or insulin glargine U100/U300) in 1,085 insulin-naïve people with type 2 diabetes in a clinical practice setting including fewer trial visits compared to the other ONWARDS phase 3a trials. Once- weekly insulin icodec was used in combination with a dosing guide app to guide titration.

The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 52 with insulin icodec compared with once-daily basal insulin analogues. From an overall baseline HbA1c of 8.9%, once-weekly insulin icodec achieved a superior reduction in estimated HbA1c of ­1.68%-points compared with ­1.31%-points for the once-daily basal insulins (estimated treatment difference: ­0.38%-points). 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 0.19 events per patient-year exposed to once-weekly insulin icodec and 0.14 events per patient-year exposed to the once-daily basal insulins.

In the trial, once-weekly insulin icodec appeared to have a safe and well-tolerated profile. potential to be an ideal insulin for people with type 2 diabetes. Novo Nordisk expects to file for regulatory approval of once-weekly insulin icodec in the US, the EU and China in the first half of 2023.

About the ONWARDS clinical development programme: The ONWARDS programme for once-weekly insulin icodec currently comprises six phase 3a global clinical trials, including a trial with real-world elements, involving more than 4,000 adults with type 1 or type 2 diabetes. ONWARDS 1 is a 78-week trial comparing the efficacy and safety of once-weekly insulin icodec with once-daily insulin glargine U100 both in combination with non-insulin anti-diabetic treatment in 984 insulin-naïve people with type 2 diabetes. Following the completion of the main phase of the trial, a 26-week extension phase is ongoing.

The results of the main phase were reported on 3 June 2022. ONWARDS 2 was a phase 3a, 26-week efficacy and safety treat-to-target trial investigating once-weekly insulin icodec vs insulin degludec in 526 people with type 2 diabetes switching from a once-daily insulin. Results were reported on 28 April 2022.

ONWARDS 3 was a 26-week trial comparing once-weekly insulin icodec with once-daily insulin degludec. The objective of the trial was to assess the efficacy and safety of insulin icodec in 588 insulin-naïve people with type 2 diabetes. Results were reported on 29 July 2022.

ONWARDS 4 was a 26-week trial comparing once-weekly insulin icodec with once-daily insulin glargine, both in combination with mealtime insulin. The objective of the trial was to assess the efficacy and safety of insulin icodec in 582 people with type 2 diabetes treated with basal and bolus insulin. Results were reported on 29 July 2022.

ONWARDS 5 was a 52-week trial comparing once-weekly insulin icodec with once-daily basal insulin (insulin degludec and insulin glargine U100 and U300) The objective of the trial was to assess the effectiveness and safety of insulin icodec, with an app providing dosing recommendation, in 1,085 insulin-naïve people with type 2 diabetes in a clinical practice setting including no upper limit at HbA1c at time of inclusion, no limitations on use of oral antidiabetic treatments and fewer planned site visits compared to the other ONWARDS phase 3a trials (every third month in accordance with recommended clinical practice) ONWARDS 6 is a 52-week trial comparing once-weekly insulin icodec with once-daily insulin degludec, both in combination with mealtime insulin. The objective of the trial is to assess the efficacy and safety of insulin icodec in 583 people with type 1 diabetes. Following the completion of the main phase of the trial, a 26-week extension phase is ongoing.

The results of the main phase were reported on 3 June 2022.