title: Comparison of stepwise addition of prandial insulin to a basal-bolus regimen when basal insulin is insufficient for glycaemic control in type 2 diabetes: results of the OSIRIS study.
abstract: OBJECTIVE
  The metabolic efficacy of adding prandial insulin in a stepwise manner to a straightforward basal-bolus regimen was compared in patients with type 2 diabetes mellitus (T2DM), suboptimally controlled by oral antidiabetic drugs (OADs) and once-daily basal insulin.
  
  
  METHODS
  In this international randomized, parallel-group, non-inferiority study, 811 patients with poorly controlled type 2 diabetes using basal insulin were switched to insulin glargine (GLAR) for 6 months while continuing OADs. Patients with HbA(1c) > 7% and FPG < 120 mg/dL (n=476) were then randomized to either group 1, GLAR+metformin (MET)+3×insulin glulisine (GLU), group 2, GLAR+MET+1-3×GLU, or group 3, GLAR+MET+insulin secretagogue (IS)+1-3×GLU, for 12 months. Objectives were to show the non-inferiority of efficacy of group 2 vs group 1 and vs group 3. Non-inferiority of group 2 vs group 1 was concluded if the upper limit of the 95% confidence interval (CI) for the HbA(1c) difference was ≤ to 0.4%.
  
  
  RESULTS
  The adjusted HbA(1c) difference of group 2 vs 1 for the per-protocol population crossed the non-inferiority margin (0.228, 95% CI: -0.018-0.473). There was significantly less weight gain in group 2 compared with group 1, but adverse events were otherwise similar between the two groups. In patients with HbA(1c) < 8% at baseline, non-inferiority was achieved in group 2 vs group 1.
  
  
  CONCLUSIONS
  Although non-inferiority was not achieved, stepwise intensification of GLU added to GLAR showed efficacy close to that of the basal-bolus approach and with significantly less weight gain.
authors.affiliation: Department of Diabetology, University Hospital Sainte-Marguerite, 270, boulevard de Sainte-Marguerite, 13009 Marseille, France. denis.raccah@ap-hm.fr
authors.forename: D
authors.initials: D
authors.lastname: Raccah
authors.forename: T J
authors.initials: TJ
authors.lastname: Haak
authors.forename: D
authors.initials: D
authors.lastname: Huet
authors.forename: L
authors.initials: L
authors.lastname: Monnier
authors.forename: D
authors.initials: D
authors.lastname: Robertson
authors.forename: P
authors.initials: P
authors.lastname: Labard
authors.forename: J
authors.initials: J
authors.lastname: Soler
authors.forename: A
authors.initials: A
authors.lastname: Penfornis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; C479079:insulin glulisine