Novo Nordisk Announces Superior Efficacy of Once-Weekly Insulin Icodec Over Insulin Glargine U100 in Phase IIIa Trial for Type 2 Diabetes

On June 24, Novo Nordisk announced the Phase IIIa clinical trial data of once-weekly ultra-long-acting insulin icodec for the treatment of adults with type 2 diabetes at the ADA conference, which was simultaneously published in The New England Journal of Medicine.

This 78-week randomized, open-label, Phase IIIa trial (including a 52-week primary trial period and a 26-week extension period, plus a 5-week follow-up period) enrolled insulin-naïve adults with type 2 diabetes (HbA1c levels of 7-11%). Participants were randomly assigned in a 1:1 ratio to receive either once-weekly insulin icodec or once-daily insulin glargine U100. The primary endpoint was the change in HbA1c levels from baseline to Week 52; the confirmed secondary endpoint was the percentage of time spent within the glucose range of 70 to 180 mg/dL (3.9 to 10.0 mmol/L) during Weeks 48 to 52.

Each group included 492 subjects, and the baseline characteristics of the two groups were similar. The mean reduction in HbA1c levels at 52 weeks was greater in the icodec group than in the glargine U100 group (icodec decreased from 8.50% to 6.93% [mean change,−1.55%], the percentage of insulin glargine U100 decreased from 8.44% to 7.12% [average change,−1.35%]); the estimated intergroup difference was -0.19%, 95% CI: -0.36 to -0.03, confirming the non-inferiority (P<0.001) and superiority (P=0.02) of icodec.

The percentage of time with blood glucose levels maintained within the range of 70–180 mg/dL was significantly higher in the icodec group than in the glargine U100 group (71.9% vs. 66.9%; estimated between-group difference, 4.27% [95% CI, 1.92–6.62]; P<0.001), confirming superiority. At week 52, the combined rate of clinically significant or severe hypoglycemia in the icodec group was 0.30 events per person-year versus 0.16 events per person-year in the glargine U100 group (estimated rate ratio, 1.64). By week 83, the average annual exposure-adjusted incidence rates were 0.30 and 0.16 for the two groups, respectively. No new safety signals were identified, and the incidence of adverse events was similar between the two groups.

Icodec is an ultra-long-acting insulin formulation designed by Novo Nordisk based on the oral insulin OI338, with a half-life of up to 196 hours in the human body. Its core design includes: ① replacing the 18C long-chain fatty acid with a 20C long-chain fatty acid to enhance the molecule's binding affinity to human serum albumin; ② replacing Tyr (tyrosine) at position 16 of the B chain with His (histidine) to reduce the molecule's affinity for the human insulin receptor. The product has been submitted for marketing approval in the United States, the European Union, and China (see: ).

In addition to icodec monotherapy and icodec + insulin, Novo Nordisk has also developed a combination therapy of icodec + semaglutide (see: ).

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