Poster Presentation The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2017

Efficacy and safety of fast-acting insulin aspart are maintained over 52 weeks: comparison with insulin aspart in onset 1 (#225)

Stephen Twigg 1 , Chantal Mathieu 2 , Bruce Bode 3 , Edward Franek 4 , Athena Philis-Tsimikas 5 , Ludger Rose 6 , Tina Graungaard 7 , Anne Birk Østerskov 7 , David Russell-Jones 8
  1. The University of Sydney, Sydney, NSW, Australia
  2. Clinical and Experimental Endocrinology, UZ Leuven, Leuven, Belgium
  3. Atlanta Diabetes Associates, Atlanta, Georgia, USA
  4. Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland
  5. Scripps Whittier Diabetes Institute, San Diego, California, USA
  6. Diabetes Research Center, Münster, Germany
  7. Novo Nordisk A/S, Søborg, Denmark
  8. Department of Endocrinology & Diabetes, Royal Surrey County Hospital, Guildford, UK

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.

 

ClinicalTrials.gov: NCT01831765