onset 1 was a phase 3a trial evaluating fast-acting insulin aspart (FA) in adults with type 1 diabetes (T1D) over 52 weeks in two 26-week periods. Subjects were randomised to double-blind mealtime FA, insulin aspart (IAsp) or open-label post-meal FA, each with insulin detemir for the first 26 weeks. Subjects on mealtime FA (n=381) and IAsp (n=380) continued to the additional 26-week period, aimed to assess long-term safety and efficacy.
After 52 weeks, mean HbA1c change from baseline (−0.08% [FA] vs. +0.01% [IAsp]) showed a significant estimated treatment difference (ETD) [95% confidence interval (CI)] favouring FA (ETD: −0.10% [−0.19;−0.00]). Change from baseline in 1-h postprandial plasma glucose (PPG) increment after meal test was −1.05 mmol/L (FA) vs. −0.14 mmol/L (IAsp) (ETD: −0.91 mmol/L [−1.40;−0.43]; −16.48 mg/dL [−25.17;−7.80]). A similar trend toward better efficacy with FA vs. IAsp was seen in change from baseline in 2-h PPG increment after meal test (ETD [95% CI]: −0.42 mmol/L [−1.11;0.27]; −7.60 mg/dL [−19.98;4.78]). Mean 7-9-7-point self-measured plasma glucose profiles were significant in favour of FA (ETD: −0.23 mmol/L [−0.46;−0.00]; −4.14 mg/dL [−8.23;−0.06]). Median total insulin dose was 0.77 U/kg (FA) vs. 0.83 U/kg (IAsp). No difference was observed for body weight change (+1.18 kg [FA] vs. +1.05 kg [IAsp]; ETD: 0.13 kg [−0.38;0.65]).
After 52 weeks, adverse events were similar between FA and IAsp, and as expected for IAsp. Severe or blood glucose-confirmed hypoglycaemia rates (plasma glucose <3.1 mmol/L [56 mg/dL]) were similar with FA (53.29 events/patient-year) vs. IAsp (53.19 events/patient-year) (estimated ratio: 1.01 [95% CI: 0.88;1.15]).
No long-term safety issues were identified with FA. Glycaemic control was significantly improved after 52 weeks with FA vs. IAsp. Approaching a profile closer to physiology with FA achieves lower PPG and HbA1c in T1D compared with IAsp.