Once-Weekly Injections of Icodec Insulin Improves Glycemic Control in Type 2 Diabetes Compared to Once-Daily Alternative


Not only was the glycemic control improved, but those who received once-weekly injections of icodec insulin had spent more time in the target glycemic range compared those who received once-daily injections.

A common treatment guideline for type 2 diabetes is either a once- or twice-daily injection of basal insulin. Clinical evidence supports the benefits of reducing the number of injections and patients with type 2 diabetes report that they prefer receiving less injections.

Man injecting insulin | Syda Productions | stock.adobe.com

Man injecting insulin | Syda Productions | stock.adobe.com

In a phase 3a trial, investigators evaluated the effects of 2 different types of insulin on 984 patients with type 2 diabetes who had not previously received insulin. During the study, which consisted of a 78-week randomized, open-label, treat-to-target trial (including a 52-week main phase, a 26-week extension phase, and a 5-week follow-up period), the participants were split into 2 groups of 492 individuals. The first group received once-weekly injections of insulin icodec (starting dose 70 U per week; Aweegli, Novo Nordisk), and the second group received once-daily injections of glargine U100 (starting dose 10 U per day). The first endpoint was the patients’ glycated hemoglobin level from baseline to week 52, with a second endpoint being the percentage of time spent in the glycemic range of 70 to 180 mg per deciliter. Due to the nature of a treat-to-target trial, the insulin was dose-adjusted to allow patients to reach their target blood glucose levels.

Further, all 984 participants had received at least one dose of trial treatment, with 954 (97.0%) reaching the week 52 visit without discontinuing treatment (475 [96.5%] in the icodec group and 479 [97.4%] in the glargine U100 group). Additionally, 953 participants (96.8%) completed the week 78 visit (476 [96.7%] in the icodec group and 477 [97.0%] in the glargine U100 group) without permanent treatment discontinuation, of whom 466 (94.7%) received icodec and 472 (95.9%) received glargine U100.

The study results showed that overall glycemic control was better in patients who received the once-weekly insulin icodec injections over those who received once-daily insulin glargine U100. Further, the mean reduction of glycated hemoglobin level at 52 weeks was greater in the icodec group (8.50% to 6.93%; mean change, -1.55%) versus the glargine U100 group (8.44% to 7.12%; mean change, -1.35%). Further, the time spent within the glycemic range of 70 to 180 mg per deciliter was higher with icodec (71.9%) than with glargine U100 (66.9%).

At weeks 52 and 78, more participants receiving icodec than those receiving glargine U100 reached a glycated hemoglobin level below 7% without clinically significant or severe hypoglycemia. Patients in the icodec group also had spent more time in the target glycemic range than those in the glargine U100 group (an additional 1 hour 1 minute per day versus an additional 1 hour and 4 minutes per day).

Despite the improvements in glycemic control, there was 1 episode of severe hypoglycemia that had occurred within the icodec group, and 7 within the glargine U100 group during the trial. Additionally, a total of 1882 adverse events (AEs) occurred in 397 participants receiving icodec, and 1823 events occurred in 389 participants receiving glargine U100. Most AEs were nonserious, mild, or moderate in severity, or were assessed by the investigator as being unlikely to be related to the trial’s treatment. Similarly, the 95 and 119 serious AEs in the icodec and glargine U100 groups were unlikely related to trial treatment as well.

However, with these results, the study investigators noted that the limitations of this study include the lack of continuous glucose monitoring throughout the duration of the trial and the study’s design, which was not double-blind to limit the required number of injections that would burden the participants throughout the trial’s duration.


Rosenstock J, Bain SC, Gowda A, et al. Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin. N Engl J Med. 2023; 389(4):297-308. doi: 10.1056/NEJMoa2303208.

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