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

OBJECTIVE This multicenter, double-blind, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in adults with type 2 diabetes receiving basal insulin and oral antidiabetic agents. RESEARCH DESIGN AND METHODS The primary end point was HbA(1c) change from baseline after 26 weeks' treatment. After an 8-week run-in to optimize basal insulin, subjects were randomized (1:1) to mealtime faster aspart (n=345) or IAsp(n =344), titrated using a simple daily patient-driven algorithm, plus insulin glargine U100 and metformin. RESULTS HbA(1c) change was -1.38% (faster aspart) and -1.36% (IAsp); mean HbA(1c) was 6.6% for both groups. Faster aspart demonstrated noninferiority versus IAsp in reducing HbA(1c) (estimated treatment difference [ETD] [95% CI] -0.02% [-0.15; 0.10]). Both treatments improved postprandial plasma glucose (PPG) control; the PPG increment (liquid meal test) was statistically significant in favor of faster aspart after 1 h (ETD [95% CI] -0.59 mmol/L [-1.09; -0.09]; -10.63mg/dL [-19.56; -1.69]; P=0.0198), but not after 2-4 h. Change from baseline in fasting plasma glucose, body weight, and overall severe/blood glucose-confirmed hypoglycemia rates (rate ratio [RR] [95% CI] 1.09 [0.88; 1.36]) were similar between treatments. Postmeal hypoglycemia (022 h) rates were 2.27 (faster aspart) and 1.49 (IAsp) per patient-year of exposure (RR [95% CI] 1.60 [1.13; 2.27]). CONCLUSIONS Faster aspart and IAsp were confirmed noninferior in a basal-bolus regimen regarding change from baseline in HbA(1c). Faster aspart improved 1-h PPG with no differences in 224-h PPG versus IAsp. Overall hypoglycemia rates were similar except for an increase in 022-h postmeal hypoglycemia with faster aspart.