title: A stepwise approach to insulin therapy in patients with type 2 diabetes mellitus and basal insulin treatment failure.
abstract: OBJECTIVE
  To determine whether 1 or 2 preprandial injections before the meals of greatest glycemic impact can be as effective as 3 preprandial injections in patients with type 2 diabetes mellitus and basal insulin treatment failure.
  
  
  METHODS
  This was an open-label, parallel-group, 1:1:1 randomized study of adults with type 2 diabetes mellitus on oral antidiabetic drugs with glycated hemoglobin (A1C) levels of 8.0% or greater. After a 14-week run-in with insulin glargine, patients with an A1C level greater than 7.0% were randomly assigned to 1, 2, or 3 time(s) daily insulin glulisine for 24 weeks. Changes in A1C from randomization to study end; percentage of patients achieving an A1C level less than 7.0%; changes in A1C, fasting glucose concentrations, and weight at individual study points; and safety (adverse events and hypoglycemia) were assessed throughout the study.
  
  
  RESULTS
  Three hundred forty-three of 631 patients (54%) completing the run-in phase with insulin glargine were randomly assigned to treatment arms. During the randomization phase, A1C reductions with insulin glulisine once or twice daily were noninferior to insulin glulisine 3 times daily (confidence intervals: -0.39 to 0.36 and -0.30 to 0.43; P>.5 for both). However, more patients met the target A1C with 3 preprandial injections (46 [46%]) than with 2 injections (34 [33%]) or 1 injection (30 [30%]). Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance.
  
  
  CONCLUSIONS
  This study provides evidence that initiation of prandial insulin in a simplified stepwise approach is an effective alternative to the current routine 3 preprandial injection basal-bolus approach.
authors.affiliation: Charles Drew University, Los Angeles, CA, USA. mayerdavidson@cdrewu.edu
authors.forename: Mayer B
authors.initials: MB
authors.lastname: Davidson
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Tanenberg
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Vlajnic
authors.forename: Pricilla
authors.initials: P
authors.lastname: Hollander
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C479079:insulin glulisine