title: Comparison of 2 intensification regimens with rapid-acting insulin aspart in type 2 diabetes mellitus inadequately controlled by once-daily insulin detemir and oral antidiabetes drugs: the step-wise randomized study.
abstract: OBJECTIVE
  To compare the efficacy and safety of 2 intensification strategies for stepwise addition of prandial insulin aspart in patients with type 2 diabetes mellitus treated with insulin detemir.
  
  
  METHODS
  This randomized, controlled, parallel-group, open-label, 48-week trial compared the stepwise addition of insulin aspart to either the largest meal (titration based on premeal glucose values [SimpleSTEP]) or to the meal with the largest prandial glucose increment (titration based on postmeal glucose values [ExtraSTEP]) in patients with type 2 diabetes inadequately controlled on basal insulin and oral antidiabetes drugs. After 12 weeks of basal insulin detemir dosage optimization, participants with a hemoglobin A1c level of 7% or greater entered three 12-week treatment periods with stepwise addition of a first insulin aspart bolus, then a second, and then a third, if hemoglobin A1c remained at 7% or greater after 12 and 24 weeks of treatment, respectively. Endpoints included hemoglobin A1c (primary endpoint), fasting plasma glucose, self-measured plasma glucose, adverse events, and hypoglycemia.
  
  
  RESULTS
  Two hundred ninety-six patients were randomly assigned to treatment with insulin aspart in the SimpleSTEP (n = 150) and ExtraSTEP (n = 146) groups. Hemoglobin A1c decreased by approximately 1.2% in both groups, to 7.5 ± 1.1% (Simple-STEP) and 7.7 ± 1.2% (ExtraSTEP) at end of trial (estimated treatment difference, SimpleSTEP - ExtraSTEP: -0.06% [95% confidence interval, -0.29 to 0.17]). Self-measured plasma glucose levels decreased with both regimens. At trial end, approximately 75% of patients in each group were using 3 prandial injections. The frequency of adverse events and hypoglycemia was low and similar between groups.
  
  
  CONCLUSIONS
  The SimpleSTEP and ExtraSTEP strategies for stepwise addition of insulin aspart to 1 or more meals were equally effective at intensifying therapy in patients with type 2 diabetes not achieving glycemic control on basal insulin and oral antidiabetic drugs.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, University of Miami Miller School of Medicine, Miami, Florida, USA. Lmeneghi@med.miami.edu
authors.forename: Luigi
authors.initials: L
authors.lastname: Meneghini
authors.forename: Henriette
authors.initials: H
authors.lastname: Mersebach
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.forename: Anne Louise
authors.initials: AL
authors.lastname: Svendsen
authors.forename: Kjeld
authors.initials: K
authors.lastname: Hermansen
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D061266:Insulin, Short-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D061266:Insulin, Short-Acting; D000069057:Insulin Detemir