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)

Diabetes Care. 2017 Jul;40(7):943-950. doi: 10.2337/dc16-1771. Epub 2017 Mar 29.

Abstract

Objective: 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.

Research design and methods: The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)-each with insulin detemir.

Results: HbA1c 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 HbA1c versus IAsp (P = 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]; P < 0.0001) and 2 h (-0.67 mmol/L [-1.29; -0.04], -12.01 mg/dL [-23.33; -0.70]; P = 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.

Conclusions: Faster aspart effectively improved HbA1c, 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 HbA1c noninferior to that obtained with mealtime IAsp.

Trial registration: ClinicalTrials.gov NCT01831765.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemia / drug therapy
  • Insulin Aspart / therapeutic use*
  • Insulin Detemir / therapeutic use
  • Male
  • Meals
  • Middle Aged
  • Postprandial Period

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin Detemir
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT01831765