Adults with type 2 diabetes achieved remarkable improvements in glycemic control using a novel combination of once-weekly insulin icodec and continuous glucose monitoring (CGM) in the ONWARDS 9 phase 3b trial. The single-arm study demonstrated significant reductions in HbA1c levels and substantial improvements in time in range over 26 weeks of treatment.
Trial Design and Participants
The ONWARDS 9 trial enrolled 51 adults aged 18 years and older with type 2 diabetes and baseline HbA1c levels between 7% and 11%. Participants had a mean age of 61.3 years and received insulin icodec (Novo Nordisk) while using the FreeStyle Libre 2 CGM (Abbott Diabetes Care) throughout the 26-week study period.
Insulin icodec was initiated during a 2-week run-in period with a 700 U/mL dose, with weekly dose adjustments based on pre-breakfast CGM values prior to titration. This approach represents a departure from traditional finger-stick glucose monitoring for insulin titration.
Significant Glycemic Improvements
The study achieved its primary endpoint with HbA1c levels declining from 8.18% at baseline to 7% at 26 weeks (P < .0001). By the end of treatment, 92% of participants achieved an HbA1c of less than 8%, while 46% reached the more stringent target of less than 7%. Notably, 42% of participants achieved an HbA1c below 7% without experiencing clinically significant or severe hypoglycemia during the final 12 weeks of therapy.
Time in range, defined as glucose levels between 70 mg/dL and 180 mg/dL, showed dramatic improvement from 54.4% at baseline to 76.4% in the final four weeks of treatment (P < .0001). This increase translated to an additional 5 hours and 11 minutes of optimal glucose control per day for participants.
Time above range, indicating glucose levels exceeding 180 mg/dL, decreased substantially from 45.2% at baseline to 22.9% during weeks 22-26 of insulin icodec therapy. Time below range with glucose levels below 54 mg/dL remained very low throughout the study, at 0.03% at baseline and 0.04% in the final four weeks.
Safety Profile and Adverse Events
The combination therapy demonstrated an excellent safety profile with no severe hypoglycemia episodes occurring during the entire study period. Researchers documented 13 clinically significant hypoglycemic episodes among 10 participants, representing a low incidence rate.
The trial recorded 113 adverse events total, with only 10 considered probably or possibly related to insulin icodec treatment. No adverse events resulted in participant withdrawal from the study. Two serious adverse events were reported, both deemed unlikely to be related to insulin icodec therapy.
A post hoc exploratory analysis revealed that time in range was marginally higher and time above range marginally lower on days 2-4 following insulin icodec administration. Time below range with glucose below 70 mg/dL showed slight increases on days 3 and 4 after treatment. Glycemic variability, measured through coefficient of variation, increased modestly from 25.52% at baseline to 27.96% in the trial's final four weeks.
Clinical Implications and Future Directions
Richard M. Bergenstal, MD, executive director of the International Diabetes Center at HealthPartners Institute in Minneapolis, emphasized the potential impact of this combination approach on diabetes management. "In the future, we might not be looking at just fasting glucose," Bergenstal told Healio. "We might just look at what's your lowest glucose of the day and let's titrate basal insulin off that. You can never do that with finger-stick glucose, but you can do that with CGM."
Bergenstal highlighted how CGM data could enable more personalized diabetes management: "Now you have the rest of the data [beyond fasting glucose] to see if that titration I'm about to make is really the right thing for this patient. This is getting into precision medicine."
The researcher also suggested potential synergies with existing therapies, particularly GLP-1 receptor agonists. "[GLP-1s] are so good on [lowering] post-meal glucose and they lower the fasting glucose a little," Bergenstal explained. "But if you are still having elevated fasting glucose... or your HbA1c is still up and you're on a GLP-1 or GIP/GLP-1 dual agonist, this could be a perfect combination."
Regulatory Status and Market Outlook
Insulin icodec has not yet received FDA approval. The agency issued a complete response letter in July 2024 following an FDA advisory committee vote of 7-4 against recommending approval for adults with type 1 diabetes. The FDA has not yet reviewed data for type 2 diabetes applications.
Bergenstal suggested that the ONWARDS 9 findings could support future FDA approval efforts and may encourage broader insulin adoption among people with type 2 diabetes who currently rely on finger-stick monitoring. He advocated for future trials exploring the combination of GLP-1 therapies, insulin icodec, and CGM technology.
The study findings were presented at the International Conference on Advanced Technologies & Treatments for Diabetes and published in March in Diabetes Technology & Therapeutics, representing an important step toward advancing precision diabetes management approaches.
