Insulin icodec is a novel albumin-bound insulin that, once injected, is slowly released from the albumin at a rate making it suitable for once-weekly administration.
Here we round up the phase 3 trials of this novel basal insulin. All the trials are treat-to-target, with one double-blind, double-dummy (ONWARDS 3), and the remainder open label. One trial (ONWARDS 6) focuses on people with type 1 diabetes, but the other trials are all in people with type 2 diabetes.
The drug manufacturer Novo Nordisk is the sponsor of all trials.
ONWARDS 1: Published
Trial population: People with type 2 diabetes, insulin-naïve but taking at least one non-insulin antihyperglycemic medication | Comparator treatment: Daily insulin glargine |
In this trial, insulin icodec achieved both noninferiority and superiority to insulin glargine over 52 weeks of use.
The results, reported in The New England Journal of Medicine in July 2023, show the average glycated hemoglobin (HbA1c) reductions were 1.55% versus 1.35%, respectively.
There was less than one hypoglycemic event per person-year of exposure for both groups, but the rate of combined clinically significant or severe hypoglycemic episodes was slightly higher for insulin icodec than insulin glargine. Overall, the incidences of adverse events were similar for the two groups.
Related news story: ONWARDS 1: Weekly insulin icodec outperforms daily insulin glargine U100 in type 2 diabetes
ONWARDS 2: Published
Trial population: People with type 2 diabetes, already using basal insulin, with/without other antihyperglycemic medications | Comparator treatment: Daily insulin degludec |
This trial, published in May 2023 in The Lancet Diabetes and Endocrinology, again reported both noninferiority and superiority of icodec to the comparator daily insulin, in this case degludec. The 526 participants had inadequate control of their type 2 diabetes with once-daily or twice-daily basal insulin and all used insulin aspart for mealtime boluses throughout the 26-week trial.
The average HbA1c reductions were 0.93% with insulin icodec and 0.71% with insulin degludec. The rate of combined severe or clinically significant hypoglycemic events was numerically but not statistically significantly higher in the insulin icodec group than the insulin degludec group, with less than one severe or clinically significant hypoglycemic event per patient-year of exposure in both groups.
Related news story: ONWARDS 2: Weekly insulin icodec superior to degludec in type 2 diabetes
ONWARDS 3: Published
Trial population: People with type 2 diabetes, insulin-naïve but taking at least one non-insulin antihyperglycemic medication | Comparator treatment: Daily insulin degludec |
The results of ONWARDS 3, published in The Journal of the American Medical Association in June 2023, revealed insulin icodec to be both noninferior and superior to insulin degludec, with average HbA1c reductions of 1.6% and 1.4% from baseline to week 26, respectively.
The combined rate of severe or clinically significant hypoglycemia was numerically higher in the icodec group from week 0 to 31 and statistically higher from week 0 to 26, but there was less than one event per patient-year of exposure in both groups.
ONWARDS 4: Published
Trial population: People with long-standing type 2 diabetes, already using a basal–bolus insulin regimen with/without other antihyperglycemic medications | Comparator treatment: Daily insulin glargine |
As reported in May 2023 in The Lancet, after 26 weeks of treatment insulin icodec achieved noninferiority to insulin glargine but not superiority, with average HbA1c reductions of 1.16% and 1.18%, respectively. Participants all used insulin aspart as their bolus insulin. Rates of combined severe and clinically significant hypoglycemia were similar for both treatment groups..
ONWARDS 5: Published
Trial population: People with type 2 diabetes, insulin-naïve but taking at least one non-insulin antihyperglycemic medication | Comparator treatment: Daily insulin glargine (U100 or U300), daily insulin degludec |
The ONWARDS 5 trial explored insulin icodec use in a setting closer to standard clinical practice than the other trials in the series. Study visits were every 3 months, there was no upper limit on HbA1c, and participants used a dosing guide app to guide titration of insulin icodec.
The findings, reported in Annals of Internal Medicine in September 2023, showed both noninferiority and superiority for insulin icodec versus the daily insulins. The average HbA1c reductions were 1.68% and 1.31%, respectively. Rates of severe or clinically significant hypoglycemia were similar for both insulin icodec and the daily insulins and there was less than one event per patient-year of exposure in both groups.
Related news story: ONWARDS 5: Weekly insulin icodec with app shows real-world promise for type 2 diabetes
ONWARDS 6: Published
Trial population: People with type 1 diabetes, already using a basal–bolus insulin regimen for at least 1 year | Comparator treatment: Daily insulin degludec |
The results of the only trial in people with type 1 diabetes were published in October 2023 in The Lancet, revealing that insulin icodec achieved noninferiority to insulin degludec over 26 weeks of use, with respective HbA1c reductions of 0.47% and 0.51%. Participants all used insulin aspart as their bolus insulin.
However, insulin icodec was associated with a significant increase in the rate of severe or clinically significant hypoglycemia compared with degludec, at rates of 19.93 versus 10.37 events per person–year.
Related news story: ONWARDS 6: Weekly insulin icodec noninferior to daily degludec in type 1 diabetes
ONWARDS 9: Active, not recruiting
Trial population: People with type 2 diabetes, insulin-naïve but taking at least one non-insulin antihyperglycemic medication | Comparator treatment: None |
NCT05823948; estimated primary study completion March 2024 | |
The ONWARDS 9 trial will monitor the change in HbA1c in 50 participants who will wear a flash glucose monitor and scan it four times daily in addition to receiving insulin icodec for 26 weeks.
Provided by Springer Medicine © 2023 Springer Medizin Verlag GmbH, part of the Springer Nature Group