Faster aspart versus insulin aspart as part of a basal-bolus regimen in inadequately controlled type 2 diabetes: The onset 2 trial

Abstract

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 HbA1c 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 patientdriven algorithm, plus insulin glargine U100 and metformin. Results: HbA1c change was-1.38% (faster aspart) and-1.36% (IAsp); mean HbA1c was 6.6% for both groups. Faster aspart demonstrated noninferiority versus IAsp in reducing HbA1c (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]-0.59mmol/L [-1.09;20.09];-10.63mg/dL [-19.56;-1.69]; P = 0.0198), but not after 2-4 h. Change frombaseline in fasting plasmaglucose, bodyweight, 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 (0-2 h) rateswere 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 HbA1c. Faster aspart improved 1-h PPG with no differences in 2-4-h PPG versus IAsp. Overall hypoglycemia rates were similar except for an increase in 022-h postmeal hypoglycemia with faster aspart.