title: 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 HbA1cafter 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.
  
  
  
  HbA1cwas 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 HbA1cversus 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.
  
  
  
  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 HbA1cnoninferior to that obtained with mealtime IAsp.
authors.affiliation: Diabetes and Endocrinology, Royal Surrey County Hospital, and University of Surrey, Guildford, U.K. davidrussell-jones@nhs.net.
authors.forename: David
authors.identifier: 0000-0002-9490-2480
authors.initials: D
authors.lastname: Russell-Jones
authors.affiliation: Atlanta Diabetes Associates, Atlanta, GA.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Bode
authors.affiliation: Department of Endocrinology, Diabetology, and Metabolism, Antwerp University Hospital, Antwerp, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: De Block
authors.affiliation: Mossakowski Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Edward
authors.initials: E
authors.lastname: Franek
authors.affiliation: Department of Oncology and Metabolism, University of Sheffield, Sheffield, U.K.
authors.forename: Simon R
authors.identifier: 0000-0002-2425-9565
authors.initials: SR
authors.lastname: Heller
authors.affiliation: Clinical and Experimental Endocrinology, University Hospital Leuven, Catholic University of Leuven, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.affiliation: Scripps Whittier Diabetes Institute, Scripps Health, San Diego, CA.
authors.forename: Athena
authors.initials: A
authors.lastname: Philis-Tsimikas
authors.affiliation: Institute of Diabetes Research, Münster, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Rose
authors.affiliation: Section of Endocrinology and Metabolism, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Woo
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Anne Birk
authors.initials: AB
authors.lastname: Østerskov
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Tina
authors.initials: T
authors.lastname: Graungaard
authors.affiliation: International Diabetes Center at Park Nicollet, Minneapolis, MN.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Bergenstal
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D061267:Insulin Aspart / Q000627:therapeutic use*; D000069057:Insulin Detemir / Q000627:therapeutic use; D008297:Male; D062407:Meals; D008875:Middle Aged; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D061267:Insulin Aspart; D000069057:Insulin Detemir