Fast-Acting Insulin Aspart Improves Glycemic Control in Basal-Bolus Treatment for Type 1 Diabetes: Results of a 26-Week Multicenter, Active-Controlled, Treat-to-Target, Randomized, Parallel-Group Trial (onset 1).

Abstract

This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus conventional insulin aspart (IAsp) in adults with type 1 diabetes. The primary end point was change from baseline in HbA_1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (<i>n</i> = 381), IAsp (<i>n</i> = 380), or open-label postmeal faster aspart (<i>n</i> = 382)-each with insulin detemir. HbA_1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart-IAsp, mealtime, -0.15% [95% CI -0.23; -0.07], and postmeal, 0.04% [-0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA_1c versus IAsp (<i>P</i> = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD -1.18 mmol/L [95% CI -1.65; -0.71], -21.21 mg/dL [-29.65; -12.77]; <i>P</i> < 0.0001) and 2 h (-0.67 mmol/L [-1.29; -0.04], -12.01 mg/dL [-23.33; -0.70]; <i>P</i> = 0.0375) after the meal test; superiority to IAsp for the 2-h PPG increment was confirmed. The overall rate of severe or blood glucose-confirmed (plasma glucose <3.1 mmol/L [56 mg/dL]) hypoglycemic episodes and safety profiles were similar between treatments. Faster aspart effectively improved HbA_1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA_1c noninferior to that obtained with mealtime IAsp.