Adding fast‐acting insulin aspart to basal insulin significantly improved glycaemic control in patients with type 2 diabetes: A randomized, 18‐week, open‐label, phase 3 trial (onset 3)

AIM: To confirm glycaemic control superiority of mealtime fast‐acting insulin aspart (faster aspart) in a basal–bolus (BB) regimen vs basal‐only insulin. MATERIALS AND METHODS: In this open‐label, randomized, 18‐week trial (51 sites; 6 countries), adults (n = 236) with inadequately controlled type 2 diabetes (T2D; mean glycosylated haemoglobin [HbA1c] ± SD: 7.9% ± 0.7% [63.1 ± 7.5 mmol/mol]) receiving basal insulin and oral antidiabetic drugs underwent 8‐week optimization of prior once‐daily basal insulin followed by randomization 1:1 to either a BB regimen with faster aspart (n = 116) or continuation of once‐daily basal insulin (n = 120), both with metformin. Primary endpoint was HbA1c change from baseline after 18 weeks of treatment. Secondary endpoints included: postprandial plasma glucose (PPG) change and overall PPG increment (all meals); weight; treatment‐emergent adverse events; hypoglycaemic episodes. RESULTS: HbA1c decreased from 7.9% (63.2 mmol/mol) to 6.8% (50.7 mmol/mol; BB group) and from 7.9% (63.2 mmol/mol) to 7.7% (60.7 mmol/mol; basal‐only group); estimated treatment difference [95% confidence interval] −0.94% [−1.17; −0.72]; −10.3 mmol/mol [−12.8; −7.8]; P < .0001. Reductions from baseline in overall mean 2‐hour PPG and overall PPG increment for all meals (self‐measured plasma glucose profiles) were statistically significant in favour of BB treatment (P < .0001). Severe/blood glucose confirmed hypoglycaemia rate (12.8 vs 2.0 episodes per patient‐years of exposure), total daily insulin (1.2 vs 0.6 U/kg) and weight gain (1.8 vs 0.2 kg) were greater with BB than with basal‐only treatment. CONCLUSIONS: In T2D, faster aspart in a BB regimen provided superior glycaemic control as compared with basal‐only insulin, but with an increase in the frequency of hypoglycaemia and modest weight gain.