Once-weekly semaglutide added to insulin icodec significantly cuts HbA1c by 1.23% and body weight by 3.85 kg in T2D.

Achieving optimal glycemic control in type 2 diabetes (T2D) remains challenging, particularly for individuals already on basal insulin therapy. Many patients struggle to reach target HbA1c levels, often requiring treatment intensification. Current strategies can be complex, increase hypoglycemia risk, or lead to weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) like semaglutide offer potent glucose-lowering effects, weight reduction, and low hypoglycemia risk, making them an attractive option for intensifying insulin regimens. This study explores the efficacy and safety of combining a novel once-weekly basal insulin, icodec, with once-weekly semaglutide to address these unmet needs.

The ONWARDS 8 trial was a single-arm, open-label, treat-to-target, Phase 3b study. It included 148 adults with T2D (baseline HbA1c: 7.5%-10.5%) on daily basal insulin but not a GLP-1RA. The study comprised a 26-week run-in period with once-weekly insulin icodec to optimize basal insulin control. Participants with HbA1c levels >7.0% and ≤10.5% at Week 26 (n=94) then entered a 26-week intensification period, adding once-weekly semaglutide titrated up to 1.0 mg. The primary endpoint was the change in HbA1c from Week 26 (semaglutide baseline) to Week 52.

Intensifying once-weekly icodec with once-weekly semaglutide demonstrated significant improvements in glycemic control and body weight. From baseline (Week 26) to Week 52, mean HbA1c decreased from 7.88% to 6.66%, representing an estimated mean change of -1.23%-points (95% confidence interval: -1.39, -1.07%-points; p<0.0001). This substantial reduction indicates effective glycemic management.

Statistically significant improvements were also observed in other key metabolic parameters: the 7-point self-measured blood glucose profile decreased by -1.72 mmol/L (p<0.0001), postprandial glucose increment decreased by -1.31 mmol/L (p<0.0001), and body weight was reduced by -3.85 kg (p<0.0001). Furthermore, the mean weekly icodec dose saw a relative decrease of 24% from Week 25 to Week 52, with 69.1% of participants having their icodec dose reduced by 20% at Week 26 per protocol. The rate of combined clinically significant or severe hypoglycemia was notably low at 0.24 episodes per person-year of exposure from baseline to Week 57.