title: Improved glycaemic control of thrice-daily biphasic insulin aspart compared with twice-daily biphasic human insulin; a randomized, open-label trial in patients with type 1 or type 2 diabetes.
abstract: OBJECTIVE
  This trial evaluated the potential for improving glycaemic control by intensifying a conventional twice-daily therapy with premixed human insulin (HI) to a thrice-daily regimen using premixed formulations of biphasic insulin aspart (BIAsp) in patients with type 1 or type 2 diabetes.
  
  
  METHODS
  This was a multicentre, open-label, parallel group trial. After a 4-week run-in period, patients were randomized 1 : 1 to 16 weeks of treatment. A total of 748 patients were screened, 664 were exposed to trial drug and 604 completed the trial.
  
  
  RESULTS
  Haemoglobin A(1c), the primary efficacy endpoint, was shown to be significantly lower for the BIAsp treatment group compared with the biphasic HI (BHI) 30 group [estimated mean difference: -0.32, 95% confidence interval (CI) (-0.48; -0.16), p = 0.0001]. The average blood glucose level was significantly lower in the BIAsp group [estimated mean difference: -0.79, 95% CI (-1.17; -0.40), p = 0.0001]. There were few major hypoglycaemic episodes, 11 in the BIAsp group and 7 in the BHI 30 group. Although intensification of insulin therapy with BIAsp three times a day was associated with a higher risk of minor hypoglycaemia (relative risk = 1.58, p = 0.0038), the overall rate of minor hypoglycaemia remained low with both the BIAsp and the BHI treatments (13.1 vs. 8.3 episodes/patient year respectively). Overall safety and patient satisfaction were similar with the two insulin therapies.
  
  
  CONCLUSIONS
  This trial confirmed that a thrice-daily BIAsp regimen can safely be used to intensify treatment for patients inadequately controlled on twice-daily BHI. A treat-to-target trial is required to explore the full potential of the BIAsp regimens and evaluate their use as a viable alternative to intensification with a basal-bolus regimen.
authors.affiliation: Watford General Hospital, Watford, Herts, UK. michaelrclements@aol.com
authors.forename: M R
authors.initials: MR
authors.lastname: Clements
authors.forename: J
authors.initials: J
authors.lastname: Tits
authors.forename: B T
authors.initials: BT
authors.lastname: Kinsley
authors.forename: J
authors.initials: J
authors.lastname: Råstam
authors.forename: H H
authors.initials: HH
authors.lastname: Friberg
authors.forename: R J
authors.initials: RJ
authors.lastname: Ligthelm
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D061267:Insulin Aspart; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart