Novo Nordisk A/S announced topline results from the COMBINE 3 phase 3a trial of once-weekly IcoSema, a fixed-ratio combination of basal insulin icodec and semaglutide. COMBINE 3 was a 52-week, open-label treat-to-target trial comparing the efficacy and safety of once-weekly IcoSema versus once-daily insulin glargine U100 and insulin aspart (injected 2-4 times a day during mealtimes), dosed with or without oral glucose-lowering medications, in 679 people with type 2 diabetes inadequately controlled on daily basal insulin. The trial achieved its primary endpoint of demonstrating non-inferiority in reducing HbA1c at week 52 with once-weekly IcoSema compared with insulin glargine U100 and insulin aspart.

From an overall baseline HbA1c of 8.30%, once-weekly IcoSema achieved an estimated reduction in HbA1c of -1.47% points compared with -1.40% points for insulin glargine U100 and insulin aspart (estimated treatment difference: -0.06% points). Further, from a baseline body weight of 85.8 kg, people treated with IcoSema achieved a superior reduction in estimated change of body weight a weight loss of -3.6 kg with IcoSema and a weight gain of 3.2 kg with insulin glargine U100 and insulin aspart (estimated treatment difference: -6.7 kg). In the trial, IcoSema was superior to insulin glargine U100 and insulin aspart in estimated rates of severe or clinically significant (blood glucose below 3.0 mmol/L) hypoglycaemia, with 0.26 events per patient-year of exposure for once-weekly IcoSema and 2.18 events per patient-year of exposure for insulin glargine U100 and insulin aspart.

In the trial, once-weekly IcoSema appeared to have a safe and well-tolerated profile. The most common adverse events for people treated with IcoSema were gastrointestinal consistent with GLP-1 receptor agonist class and the vast majority were mild to moderate. COMBINE 3 is the first trial to readout in the phase 3a COMBINE programme, and results from COMBINE 1 and COMBINE 2 will be shared later this year.