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
Krzysztof Strojek, Andreas Liebl, Neha Narendra Mumbaikar, Stinne Byrholdt Søgaard, Sara Kehlet Watt, Athena Philis‐Tsimikas ABSTRACT
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