麻豆传媒

SAN DIEGO -- Investigational once-weekly insulin icodec outperformed once-daily insulin glargine U100 when it came to glycemic control in type 2 diabetes, the phase IIIa ONWARDS 1 trial found.

Over the course of 52 weeks, people with type 2 diabetes saw a greater average reduction in HbA1c with icodec compared with glargine U100 (estimated between-group difference -0.19%, 95% CI -0.36% to -0.03%), reported Julio Rosenstock, MD, of Velocity Clinical Research at Medical City in Dallas, and colleagues.

Achieving the trial's primary endpoint, this difference in HbA1c confirmed both non-inferiority and superiority of icodec. Those on icodec say a drop from 8.50% to 6.93% while those on glargine U100 saw a drop from 8.44% to 7.12% during the year.

The findings were presented at the American Diabetes Association (ADA) Scientific Sessions and simultaneously published in the .

"I feel that weekly insulins have the potential to become transformational as preferred options for basal insulin replacement in people with type 2 diabetes in need of initiation of insulin therapy," Rosenstock said during an ADA presentation. "I think that basal insulin analogues 20 years ago, 22 years ago, were transformational on how to treat type 2 diabetes with once-daily glargine or degludec, and so on."

"I think that this is déjà vu all over again," he added. "20, 25 years later we have made a huge step forward in the management of type 2 diabetes."

This glycemic control was maintained during an extension phase of the trial as well, which continued for another 26 weeks. At the end of the 78th week since randomization, icodec-treated patients had an HbA1c of 6.92% while glargine U100 patients had an A1c of 7.03%.

By the end of the 52-week period, 57.6% of icodec patients achieved an HbA1c below 7% versus 45.4% of glargine patients.

That being said, both treatment groups had similar changes in fasting plasma glucose (-60.32 mg/dL for icodec vs -60.08 mg/dL for glargine).

During weeks 48-52 of treatment, patients on icodec also spent on average 4.27% (71.9% vs 66.9%) more of time in glycemic range -- 70 to 180 mg/dL -- achieving superiority. This translated to about 1 hour and 1 minute longer per day spent in target range. This advantage was also sustained in the extension phase, as icodec patients spent 4.41% more time (1 hr 4 min longer) in target range during weeks 74-78.

Those on icodec also spent significantly less time in hyperglycemia (glucose levels over 180 mg/dL) compared with glargine U100 (-4.58%, 1 hr 6 min less time).

Icodec patients saw a small, but statistically insignificant higher rates of clinically significant or severe hypoglycemia: 0.30 events per person-year of exposure with icodec and 0.16 events per person-year of exposure with glargine U100 at week 52 (estimated rate ratio 1.64, 95% CI 0.98-2.75). Overall, the rates of adverse events were similar between the two insulin groups.

"Insulin is insulin," said Rosenstock. "When we use insulin, there always will be hypoglycemia, but we only had less than one event per year."

The 143-site open-label trial include 492 participants in both groups, all of whom had type 2 diabetes (baseline HbA1c between 7-11%) and were never previously treated with insulin. The average age was 59 and most were male. Nearly all were also on metformin, over a third were also on an SGLT2 inhibitor and/or DPP-4 inhibitor, and about 18% were on a GLP-1 receptor agonist. Nearly half were taking sulfonylureas, but sulfonylureas and glinides were the only treatments discontinued at randomization. All other antidiabetic treatments were continued throughout the trial.

The average weekly insulin dose was 214 U per week (about 31 U per day) in the icodec group and 222 U per week (about 32 U per day) in the glargine U100 group during the main phase of the trial.

Also Superior to Degludec

Adding to the 78-week trial findings were 26-week findings from the double-blind phase IIIa ONWARDS 3 trial, presented at ADA and simultaneously published in . Here, similar findings were seen among a 588-participant group comparing once-weekly icodec to once-daily insulin degludec in insulin-naïve patients with type 2 diabetes.

After 26 weeks, icodec patients saw a drop in HbA1c from 8.6% to 7.0% versus a drop from 8.5% to 7.2% in the degludec group (estimated treatment difference -0.2, 95% CI -0.3 to -0.1%). Similar to the ONWARDS 1 trial, icodec also achieving non-inferiority and superiority here.

Likewise, there were no significant differences between the icodec and degludec groups in terms of fasting plasma glucose changes or body weight.

However, icodec patients did see a significantly higher rate of level 2 or 3 hypoglycemic events during the 26-week period (0.35 vs 0.12 events per patient-year exposure, P=0.01).

"I think most importantly, people treated with icodec will only have to take one shot a week as opposed to one shot every day," said Ildiko Lingvay, MD, of the University of Texas Southwestern Medical Center in Dallas, during an ADA presentation.

Developer Novo Nordisk announced it submitted a biologics license application to the FDA in April for once-weekly insulin icodec for the treatment of diabetes, with a decision expected April 2024.

"If approved, insulin icodec will represent the first and only once-weekly basal insulin option for adults with diabetes, addressing an unmet need in treatment vs. a daily basal insulin option," according to a .