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)

Abstract

AimTo confirm glycaemic control superiority of mealtime fast‐acting insulin aspart (faster aspart) in a basal–bolus (BB) regimen vs basal‐only insulin.Materials and methodsIn 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.ConclusionsIn 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.

Fast‐acting insulin aspart versus insulin aspart in the setting of insulin degludec‐treated type 1 diabetes: Efficacy and safety from a randomized double‐blind trial

“…The improved PPG findings reported in the present study, from both meal test and SMBG, are consistent with general findings across the faster aspart clinical trial programme 14, 15, 17, 18. Furthermore, the results here specifically support the results of the onset 1 study, in which once‐ or twice‐daily detemir in conjunction with mealtime or post‐meal faster aspart was compared with the same basal regimen and mealtime IAsp 14.…”

Faster Aspart Versus Insulin Aspart as Part of a Basal-Bolus Regimen in Inadequately Controlled Type 2 Diabetes: The onset 2 Trial

“…Nonclinical data illustrate that the addition of niacinamide promotes the formation of insulin aspart monomers after subcutaneous (s.c.) injection, facilitating a more rapid rate of insulin aspart absorption across the endothelium into the blood (9). In adults with type 1 diabetes, s.c. injection of faster aspart was associated with twice as fast onset of appearance in the bloodstream (4 vs. 9 min), twofold higher insulin concentration, and 74% greater insulin action in the first 30 min versus IAsp (10) [-12.75; -7.82]; P , 0.0001) (12).…”

Weight loss in patients with type 2 diabetes receiving once‐weekly dulaglutide plus insulin lispro or insulin glargine plus insulin lispro: A post‐hoc analysis of the AWARD‐4 study across baseline body mass index subgroups

“…12,22 For patients in the AWARD-4 study who received insulin glargine, improved glycaemic control was achieved at a higher mean total daily insulin dose. This is especially relevant for patients who require a combination with prandial insulin to achieve glycaemic targets, as in the AWARD-4 study population, in which maintaining or reducing body weight may be more difficult.…”