Once-Weekly Insulin Icodec Improves Time in Range, Glycemic Control Better than Daily Insulin Degludec

Julio Rosenstock, MD
Credit: Diabetes Technology Society

A pair of studies presented at the 83rd Scientific Sessions of the American Diabetes Association (ADA 2023) highlights the potential of once-weekly insulin icodec in people with type 2 diabetes.

Results of the studies, which were analyses of the ONWARDS 1 and ONWARDS 3 phase 3a trials, suggest the once-weekly insulin icodec use was associated with greater time-in-range and similar glucose-lowering effects when compared with once-daily basal insulin, despite the reduction injections.^1,2

"Time in Range provides additional information to help us assess glycemic control and is an increasingly important tool to complement HbA1c measurements which were substantially reduced by once-weekly basal insulin icodec. In ONWARDS 1, insulin icodec allowed people to spend significantly more Time in Range, with comparable Time below Range vs. once-daily basal insulin glargine U100," said lead investigator Julio Rosenstock, MD, director of Velocity Clinical Research at Medical City Dallas and clinical professor of medicine at the University of Texas Southwestern Medical Center.³ "A once-weekly basal insulin has the potential to change how we treat people with type 2 diabetes needing basal insulin replacement."

ONWARDS 1 Data

ONWARDS 1 was designed as a 78-week, open-label efficacy and safety treat-to-target trial and launched with the intent of investigating the effects of once-weekly insulin icodec compared once-daily insulin glargine U100 in insulin-naïve adults with type 2 diabetes. With an overall population of 984 patients, who were using non-insulin antidiabetes treatment, the trial had a primary endpoint of change in HbA1C from baseline to week 52 with insulin icodec relative to insulin glargine U100.¹

Initial results of the trial indicate use of once-weekly insulin icodec was associated with a superior reduction in HbA1c compared with insulin glargine U100. Results pointed to a mean HbA1c reduction of -1.55% with once-weekly insulin icodec compared to -1.35% with insulin glargine U100 (estimated treatment difference, -0.19%).¹

At ADA 2023, Rosenstock presented data examining the effects of once-weekly insulin icodec on time in range relative to insulin glargine U100. In the analysis, results suggested use of once-weekly insulin icodec was associated with superior time in target range of 70-180 mg/dL compared with use of insulin glargine U100 from weeks 48-52 of the study (71.9% vs. 66.9%, respectively; P = .0004). Rosenstock also presented data suggesting the time below 54 mg/dL from weeks 48-52 were comparable with once-weekly insulin icodec relative to once-daily basal insulin glargine U100 (0.3% vs. 0.2%, respectively).¹

ONWARDS 3 Data

ONWARDS 3 was a double-blind 26-week efficacy and safety treat-to-target trial comparing once-weekly insulin icodec against insulin degludec among a cohort of 588 insulin-naïve adults with type 2 diabetes. In this trial, the primary endpoint of interest was change in HbA1c from baseline to week 26.²

Initial results of the trial indicate use of once-weekly insulin icodec was associated with a mean reduction in HbA1c of -1.57% compared with -1.36% with insulin degludec (estimated treatment difference, -0.21%).²

At ADA 2023, Ildiko Lingvay, MD, professor of internal medicine in the Division of Endocrinology and in the Peter O’Donnell Jr. School of Public Health at University of Texas Southwestern, presented an analysis of the trial suggesting there were no significant differences in weekly insulin dose from week 24-26 or body weight change from baseline to week 26 between the study arms. During her presentation, Lingvay noted the overall rates of level 2 or 3 hypoglycemia were numerically greater with once-weekly insulin icodec relative to insulin degludec, but this did not reach statistical significance in the on-treatment period.²

"These data reinforce our confidence in the potential of once-weekly insulin icodec," said Florian M.M. Baeres, corporate vice president of Global Medical Affairs at Novo Nordisk.³ "If approved, we believe this innovation – which would be the world's first once-weekly basal insulin – could help people living with type 2 diabetes ready to start insulin treatment by reducing the number of injections needed per week."

In their release, Novo Nordisk highlights their submission of a biologics license application (BLA) in April 2023 to the US Food and Drug Administration for once-weekly insulin icodec and the company anticipates a decision from the regulatory agency in April 2024. If approved, once-weekly insulin icodec will represent the first and only once-weekly basal insulin option for adults with diabetes.³

References:

1. Rosenstock J, Bain SC, Gowda A, et al. Improved A1C and TIR with Once-Weekly Insulin Icodec vs Insulin Glargine U100 in Insulin-Naïve T2D: ONWARDS 1.Presented at: 83rd Annual Scientific Sessions of the American Diabetes Association (ADA) 23-26 June 2023, San Diego, CA. 179-OR.
2. Lingvay I, Asong M, Desouza C, et al. Better Glycemic Control with Once-Weekly Insulin Icodec versus Once–Daily Insulin Degludec in Insulin-Naïve Type 2 Diabetes (ONWARDS 3).Presented: 83rd Annual Scientific Sessions of the American Diabetes Association (ADA) 23-26 June 2023, San Diego, CA.178-OR.
3. New data show once-weekly insulin icodec met additional endpoints in adults with type 2 diabetes in phase 3a trials. Novo Nordisk. June 24, 2023. Accessed June 25, 2023. https://www.novonordisk-us.com/content/nncorp/us/en_us/media/news-archive/news-details.html?id=166123.