Phase 2 Trial Shows Weekly Insulin Injection Outcomes Similar to Daily Injections for T2D

September 22, 2020

In individuals with type 2 diabetes with no previous insulin treatment, once-weekly injections of insulin icodec resulted in glucose-lowering efficacy and a safety profile similar to individuals who took once-daily insulin glargine U100.

In individuals with type 2 diabetes (T2D) with no previous insulin treatment, once-weekly injections of insulin icodec resulted in glucose-lowering efficacy and a safety profile similar to individuals who took once-daily insulin glargine U100. Results of the randomized double-blind trial were published in the New England Journal of Medicine.

Although the American Diabetes Association and the European Association for the Study of Diabetes recommend treatment escalation when individualized glycemic targets are not met, clinical delays in insulin initiation can take place.

“Previous data have indicated that patients with T2D would generally prefer fewer injections and greater flexibility than is typical of the current once-daily treatment option,” researchers wrote. “Therefore, reducing the number of injections could potentially increase acceptance of and adherence to insulin treatment among patients with T2D, thereby potentially improving glycemic control.”

In a phase 2 trial testing insulin icodec, a basal insulin analogue administered once-weekly, investigators compared glycemic profiles of individuals who received weekly or daily insulin injections. All patients included had poorly controlled diabetes at baseline while randomization was stratified according to dipeptidyl peptidase 4 inhibitor use.

A total of 125 patients were assigned to receive icodec plus a once-daily placebo and 122 patients were assigned to receive glargine plus a once-weekly placebo. The 26-week trial included patients with a baseline glycated hemoglobin level (A1C) of 7.0 to 9.5%.

The starting dose of icodec was 70 U once weekly, and the starting dose of glargine was 10 U once daily. Insulin doses were adjusted weekly to achieve a pre-breakfast patient-measured blood glucose target of 70 to 108 mg per deciliter (3.9 to 6.0 mmol per liter), researchers explained.

Around 97% of the icodec arm completed the trial compared with 94.3% of the glargine group.

Analyses revealed:

  • Mean (SD) A1C level in the icodec group decreased from 8.09% (0.70) at baseline to an estimated mean of 6.69% at week 26; in the glargine group, A1C level decreased from 7.96% (0.65) to 6.87%
  • Estimated mean change in A1C level from baseline at week 26 was −1.33 percentage points for icodec and −1.15 percentage points for glargine, for an estimated mean treatment difference of −0.18 percentage points (95% confidence interval [CI], −0.38 to 0.02; P=.08)
  • Estimated percentages of patients reaching an A1C level of less than 7% at week 26 were 72% in the icodec group and 68% in the glargine group (estimated odds ratio [OR], 1.20; 95% CI, 0.98 to 2.13)
  • Percentages of patients reaching an A1C level of 6.5% or less were 49% in the icodec arm and 39% in the glargine group (OR, 1.47; 95% CI, 0.85 to 2.52)
  • The observed incidence of level 1 hypoglycemia alerts was 53.6% in the icodec group and 37.7% in the glargine group
  • For both icodec and glargine, the observed incidence of combined level 2 or level 3 hypoglycemia was 16.0% and 9.8%, respectively; the observed event rates were 0.53 and 0.46 events per patient-year of exposure, respectively, with an estimated rate ratio of 1.09 (95% CI, 0.45 to 2.65)

In addition, the icodec group exhibited a lower mean patient measured A1C level at all time points compared with the glargine group. Approximately half of patients in each treatment arm experienced an adverse event (AE) throughout the trial, including reports of 2 serious AEs in 2 patients receiving icodec and 12 serious AEs in 3 patients who received glargine. However, none of the AEs were considered by investigators to be possibly or probably related to trial medications.

Reference:

Rosenstock J, Bajaj HS, Janež A, et al. Once-weekly insulin for type 2 diabetes without previous insulin treatment. N Engl J Med. Published online September 22, 2020. doi:10.1056/NEJMoa2022474