Once-weekly insulin icodec plus CGM improves glycemic control in type 2 diabetes
Key takeaways:
- Adults with type 2 diabetes lowered their HbA1c from 8.18% at baseline to 7% at 26 weeks with insulin icodec plus a CGM.
- Time in range improved by more than 20 percentage points during the study.
Once-weekly basal insulin combined with an intermittently scanned continuous glucose monitor reduced HbA1c and improved time in range for adults with type 2 diabetes, researchers reported.
In the single-arm ONWARDS 9 phase 3b trial, adults with type 2 diabetes received insulin icodec (Novo Nordisk) and used a CGM (FreeStyle Libre 2, Abbott Diabetes Care) for 26 weeks. The participants had significant improvements in glycemic control during the trial with no severe hypoglycemic events. Findings from the trial were presented at the International Conference on Advanced Technologies & Treatments for Diabetes and published in March in Diabetes Technology & Therapeutics.
Richard M. Bergenstal, MD, executive director of the International Diabetes Center, HealthPartners Institute in Minneapolis, said he believes that the use of CGM combined with once-weekly insulin could advance glycemic management for adults with insulin-treated type 2 diabetes.
“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. This was an important pilot study to show how effective CGM and basal insulin were together.”
Glycemic benefits
In ONWARDS 9, investigators enrolled 51 adults aged 18 years and older with type 2 diabetes and an HbA1c between 7% and 11% (mean age, 61.3 years). All participants received insulin icodec and used a CGM for 26 weeks. Insulin icodec was started during a 2-week run-in period with a 700 U/mL dose. Doses were adjusted each week based on pre-breakfast CGM values prior to titration.
The study group had a decline in the primary endpoint of HbA1c from 8.18% at baseline to 7% at 26 weeks (P < .0001). At the end of treatment, 92% of adults had an HbA1c of less than 8%, 46% achieved an HbA1c of less than 7% and 42% had an HbA1c of less than 7% with no clinically significant or severe hypoglycemia in the final 12 weeks of therapy.
Mean time in range with a glucose of 70 mg/dL to 180 mg/dL rose from 54.4% at baseline to 76.4% in the final 4 weeks of treatment (P < .0001). The increase in time in range was equivalent to an additional 5 hours and 11 minutes of time in range per day. Time above range with a glucose of more than 180 mg/dL dropped from 45.2% at baseline to 22.9% at 22 to 26 weeks of insulin icodec therapy. Time below range with glucose of less than 54 mg/dL was very low — 0.03% at baseline and 0.04% in the last 4 weeks of the trial.
Safety data
No severe hypoglycemia episodes occurred during the study. There were 13 clinically significant hypoglycemic episodes that occurred among 10 adults.
There were 113 adverse events in the trial, of which 10 were considered probably or possibly related to insulin icodec. No adverse events resulted in participant withdrawal. There were two serious adverse events reported, both of which were considered unlikely to be related to insulin icodec.
In a post hoc exploratory analysis, researchers examined CGM metrics by treatment day. Time in range was marginally higher and time above range marginally lower day 2 through day 4 after insulin icodec therapy. Time below range with a glucose of less than 70 mg/dL was slightly higher days 3 and 4 after insulin icodec treatment. Glycemic variability as measured through coefficient of variation rose from 25.52% at baseline to 27.96% in the trial’s final 4 weeks.
A step forward in diabetes management
Insulin icodec has not yet been approved by the FDA. As Healio previously reported, the FDA issued a complete response letter for insulin icodec in July 2024 after the FDA Endocrinologic and Metabolic Drugs Advisory Committee voted 7-4 against recommending approval of the drug for adults with type 1 diabetes during a May meeting. The FDA did not review data on adults with type 2 diabetes at the time.
Bergenstal said the findings from ONWARDS 9 may help insulin icodec earn FDA approval in the future and could have several implications on diabetes care. He said the data provided by CGM may encourage people with type 2 diabetes to use insulin, as they would not need to use finger sticks to check glucose levels every morning. Additionally, he said CGM could allow glycemic management to be individualized for each patient.
“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,” Bergenstal said. “This is getting into precision medicine.”
Bergenstal said adding a once-weekly basal insulin and CGM to GLP-1 therapy could provide greater benefits for people who are struggling to achieve their target HbA1c with a GLP-1 alone.
“[GLP-1s] are so good on [lowering] post-meal glucose and they lower the fasting glucose a little,” Bergenstal said. “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. [Insulin icodec and GLP-1s] are both once a week, patients can just take them and be on their way. I think it’s going to be powerful.”
Bergenstal said trials exploring the combination of a GLP-1, insulin icodec and CGM should be conducted in the future.
References:
For more information:
Richard M. Bergenstal, MD, can be reached at richard.bergenstal@parknicollet.com.
Perspective
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ONWARDS 9, a single-arm, multicenter, treat-to target clinical trial, demonstrated that insulin icodec plus intermittently scanned CGM improves glycemic control in adults with type 2 diabetes. Adults with type 2 diabetes lowered their HbA1c from 8.18% at baseline to 7% at 26 weeks with insulin icodec plus a CGM, and time in range was demonstrated to improve by more than 20 percentage points during the study. There was a statistically significant reduction in HbA1c of 1.17 percentage points. No severe hypoglycemic episodes were reported during the trial, and no new safety concerns for insulin icodec were identified.
This was an important pilot study to show how effective CGM and once-weekly insulin icodec are when used in combination. While once-weekly insulin icodec is not currently approved for use in the U.S., it is approved in the European Union, Canada, Australia, Japan and Switzerland for the treatment of both type 1 and type 2 diabetes and in China for the treatment of type 2 diabetes.
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Bergenstal RM. The next step: Utilizing CGM measures for insulin titration. Presented at: International Conference on Advanced Technologies & Treatments for Diabetes; March 19-22, 2025; Amsterdam (hybrid meeting).