Efficacy and Safety of Intensifying Once-Weekly Insulin Icodec Treatment With Once-Weekly Semaglutide in Adults With Type 2 Diabetes: A Single-Arm, Open-Label, Treat-to-Target, Phase 3b Trial (ONWARDS 8).

AIMS: To investigate the efficacy and safety of intensifying once-weekly insulin icodec (icodec) with once-weekly semaglutide in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: ONWARDS 8 was a single-arm, open-label, treat-to-target, Phase 3b trial comprising a 26-week icodec run-in period and a 26-week semaglutide intensification period. Eligible participants were adults with T2D (glycated haemoglobin [HbA1c]: 7.5%-10.5%) receiving daily basal insulin but not receiving a glucagon-like peptide-1 receptor agonist. Following the run-in period, participants with HbA1c levels > 7.0% and ≤ 10.5% were eligible for treatment intensification with semaglutide up to 1.0 mg. The primary endpoint was change in HbA1c from Week 26 (baseline) to Week 52. RESULTS: Overall, 148 participants were enrolled; 94 initiated semaglutide. From baseline to Week 52, mean HbA1c decreased from 7.88% (observed) to 6.66% (estimated), with an estimated mean change of -1.23%-points (95% confidence interval: -1.39, -1.07%-points; p < 0.0001). Statistically significant changes from baseline to Week 52 were observed in 7-point self-measured blood glucose profile (-1.72 mmol/L), postprandial glucose increment (-1.31 mmol/L) and body weight (-3.85 kg) (all p < 0.0001). The relative decrease in mean weekly icodec dose from Week 25 to Week 52 was 24% (69.1% of participants had their icodec dose reduced by 20% at Week 26, per protocol). From baseline to Week 57 (end of trial), the rate of combined clinically significant or severe hypoglycaemia was 0.24 episodes per person-year of exposure. CONCLUSIONS: Intensification of icodec with semaglutide was feasible, with low rates of clinically significant or severe hypoglycaemia. TRIAL REGISTRATION: NCT05813912.