The ONSET 9 trial aims to evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp), both with insulin degludec with or without metformin, in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen. This was the first trial with faster aspart to recruit only participants with long-standing (≥10 years) type 2 diabetes treated with intensive (basal-bolus) insulin therapy for ≥1 year.
The phase 3b, multicenter, active-controlled, treat-to-target, randomized, parallel-group trial consisted of a 12-week run-in period, a 16-week treatment period, and a 30-day follow-up period. The study cohort included adults ≥18 years old with type 2 diabetes for ≥10 years and had been treated with a basal-bolus insulin regimen for ≥1 year before screening and are with or without OADs. Participants were required to have an HbA1c of 7.0 - 10.0% at screening and an HbA1c ≤9.0% at randomization and were randomized 1:1 to double-blind treatment with either faster aspart or IAsp delivered in a basal-bolus regimen with once-daily insulin degludec with or without Metformin at the beginning.
Noninferiority for the change from baseline in HbA1c 16 weeks after randomization (primary end point) was confirmed for faster aspart versus IAsp where the estimated treatment difference was −0.04% [95% CI −0.11; 0.03]; −0.39 mmol/mol [−1.15; 0.37]; P < 0.001). Faster aspart was observed to be superior to IAsp for change from baseline in 1-h postprandial glucose (PPG) increment using a meal test (ETD −0.40 mmol/L [−0.66; −0.14]; −7.23 mg/dL [−11.92; −2.55]; P = 0.001 for superiority). Change from baseline in self-measured 1- h PPG increment for the mean over all meals favored faster aspart (ETD −0.25 mmol/L [−0.42; −0.09]); −4.58 mg/dL [−7.59; −1.57]; P = 0.003). The overall rate of treatment-emergent severe or blood glucose (BG)–confirmed hypoglycemia was statistically significantly lower for faster aspart versus IAsp with an estimated treatment ratio 0.81 [95% CI 0.68; 0.97].
The trial concluded that in combination with insulin degludec, faster aspart provided effective overall glycemic control, superior PPG control, and a lower rate of severe or BG-confirmed hypoglycemia compared to IAsp in adults with type 2 diabetes not optimally controlled with a basal-bolus regimen.