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

Diabetes Care. 2017 Jul;40(7):951-957. doi: 10.2337/dc16-1770. Epub 2017 May 8.

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 patient-driven 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] -0.59 mmol/L [-1.09; -0.09]; -10.63 mg/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 (0-2 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 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 0-2-h postmeal hypoglycemia with faster aspart.

Trial registration: ClinicalTrials.gov NCT01819129.

Publication types

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

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Endpoint Determination
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemia / drug therapy
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use*
  • Insulin Aspart / therapeutic use*
  • Insulin Glargine / therapeutic use
  • Male
  • Meals
  • Metformin / therapeutic use
  • Middle Aged
  • Postprandial Period

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • Insulin Glargine
  • Metformin
  • Insulin Aspart

Associated data

  • ClinicalTrials.gov/NCT01819129