title: Similar glucose control with basal-bolus regimen of insulin detemir plus insulin aspart and thrice-daily biphasic insulin aspart 30 in insulin-naive patients with type 2 diabetes: Results of a 50-week randomized clinical trial of stepwise insulin intensification.
abstract: OBJECTIVE
  This study aimed to demonstrate the non-inferiority of 50-week treatment with stepwise insulin intensification of basal-bolus insulin analogues [insulin detemir (IDet) and aspart (IAsp)] versus biphasic insulin aspart 30 (BIAsp30) in insulin-naive type 2 diabetes mellitus (T2DM) patients not controlled by oral glucose-lowering drugs (OGLDs).
  
  
  METHODS
  In this open-label multicentre, multinational, randomized, parallel-arm treat-to-target trial, 403 insulin-naive patients with T2DM in four African countries were randomized to either an IDet+IAsp (n = 200) or BIAsp1-2-3 (n = 203) treatment group. Stepwise insulin intensification was performed at the end of 14, 26 and 38 weeks, depending on HbA1c values. The primary endpoint was change in HbA1c after 50 weeks of treatment. Safety variables were hypoglycaemia incidence, occurrence of adverse events and weight gain.
  
  
  RESULTS
  Non-inferiority of the IDet+IAsp versus BIAsp1-2-3 treatment regimen was demonstrated by their similar HbA1c levels at the end of trial (IDet+IAsp: baseline 8.6%, 50 weeks 7.4%; BIAsp1-2-3: baseline 8.7%, 50 weeks 7.3%; full analysis set difference: 0.1% [95% CI: -0.1, 0.3]; per protocol: 0.2% [95% CI: -0.1, 0.4]). At week 50, 40.3 and 44.9% of patients achieved HbA1c <7.0% with IDet+IAsp and BIAsp1-2-3, respectively. The rate of overall hypoglycaemia during the trial was also similar in both groups (IDet+IAsp: 9.4 events/patient-year; BIAsp1-2-3: 9.8 events/patient-year).
  
  
  CONCLUSIONS
  Insulin initiation and intensification using IDet+IAsp was not inferior to BIAsp1-2-3 in insulin-naive patients with T2DM not controlled by OGLDs. Both regimens led to similar reductions in HbA1c values after 50 weeks of treatment.
authors.affiliation: Internal Medicine Department, Saâdna University Hospital, Setif, Algeria. Electronic address: rmalekdz@gmail.com.
authors.forename: R
authors.initials: R
authors.lastname: Malek
authors.affiliation: Department of Internal Medicine, Military Hospital of Tunis, Tunis, Tunisia.
authors.forename: F
authors.initials: F
authors.lastname: Ajili
authors.affiliation: Faculty of Medicine, Alexandria University, Alexandria, Egypt.
authors.forename: S H
authors.initials: SH
authors.lastname: Assaad-Khalil
authors.affiliation: Novo Nordisk Pharma Gulf, FZ LLC, Dubai, United Arab Emirates.
authors.forename: A
authors.initials: A
authors.lastname: Shinde
authors.affiliation: Novo Nordisk Region International Operations A/S, Zurich, Switzerland.
authors.forename: J W
authors.initials: JW
authors.lastname: Chen
authors.affiliation: Zuid-Afrikaanse Hospital, Muckleneuk, Pretoria, South Africa.
authors.forename: E
authors.initials: E
authors.lastname: Van den Berg
mesh_terms: D000328:Adult; D000349:Africa; D061265:Biphasic Insulins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000069057:Insulin Detemir / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D061265:Biphasic Insulins; D001786:Blood Glucose; D007004:Hypoglycemic Agents; C557564:insulin aspart, insulin aspart protamine drug combination 30:70; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D061267:Insulin Aspart
keywords: Basal–bolus insulin; Biphasic insulin aspart; Insulin detemir; Insulin intensification; Premixed insulin; Type 2 diabetes