medwireNews: Once-weekly insulin icodec offers superior glycemic control to once-daily insulin glargine U100 for people with type 2 diabetes who are insulin-naïve, show findings from the ONWARDS 1 trial.
“Concerns regarding daily injections and reduced treatment adherence contribute substantially to suboptimal glycemic control for many persons with type 2 diabetes,” comment Julio Rosenstock (Velocity Clinical Research at Medical City, Dallas, Texas, USA) and colleagues in The New England Journal of Medicine.
“Patients generally prefer fewer injections, and the benefits of reducing injection frequency are supported by clinical evidence.”
The phase 3a, open-label trial, which was simultaneously presented at the 83rd ADA Scientific Sessions in San Diego, California, USA, looked at the long-term effects of insulin icodec versus insulin glargine U100 over a 78-week period, comprising a 52-week main phase and a 26-week extension phase.
The 984 participants were aged a median of 59 years and had an average diabetes duration of 12 years and an average BMI of 30 kg/m2; 54–60% were men and around 65% were White. The patients could continue to take noninsulin glucose-lowering treatments for the duration of the study, with the exception of sulfonylureas and glinides.
Among the 492 people randomly assigned to receive insulin icodec 700 U/mL per week, the estimated mean glycated hemoglobin (HbA1c) level fell from 8.50% (69.4 mmol/mol) at baseline to 6.93% (52.2 mmol/mol) at week 52, a mean reduction of 1.55 percentage points.
By comparison, the estimated mean HbA1c level fell from 8.44% to 7.12% (68.7 to 54.3 mmol/mol) with glargine U100 at a dose of 100 U/mL per day, a mean reduction of 1.35 percentage points.
Rosenstock and colleagues report that the treatment difference was 0.19 percentage points in favor of insulin icodec at week 52. And this statistically significant superior reduction in HbA1c was sustained over the extension phase of the study with a treatment difference at week 78 of 0.11 percentage points, which was of borderline significance because of a small further reduction with glargine U100.
They add that between weeks 48 and 52, the people receiving insulin icodec spent a significantly greater percentage of time in the target glycemic range of 70–180 mg/dL, at 71.9% compared with 66.9% among those receiving glargine U100. This gave a between-group difference of 4.27 percentage points, which translates to “approximately 1 hour and 4 minutes more time spent in range per day with icodec,” say the investigators.
They note that the International Consensus on Time in Range recommends that more than 70% of continuous glucose monitoring measurements fall within the target glycemic range, which was achieved on average with icodec, but not with glargine U100.
The increased likelihood of achieving an HbA1c level below 7% with insulin icodec versus glargine U100 was achieved without a significantly increased risk for hypoglycemia, say Rosenstock et al.
There was a slightly higher rate of clinically significant or severe hypoglycemic episodes with insulin icodec than with glargine U100, at 0.30 events per person–year versus 0.16 events per person–year at week 52, but the team points out that “overall rates of these hypoglycemic episodes remained below one event per person-year of exposure throughout the trial, which is similar to rates reported previously in other trials of daily basal insulin analogues.”
The researchers acknowledge the limitation of the trial not being double-blind, but confirm that ONWARDS 3 has used a double-blind, double-dummy design to compare the two insulins.
They conclude that “the findings of the current trial highlight the totality of evidence for glycemic control with icodec.”
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