title: Addition of biphasic insulin aspart 30 to rosiglitazone in type 2 diabetes mellitus that is poorly controlled with glibenclamide monotherapy.
abstract: BACKGROUND
  The incidence of type 2 diabetes mellitus (DM) is rapidly increasing worldwide. Results from large-scale studies show that tight blood glucose (BG) control improves the outcome of patients with type 2 DM.
  
  
  OBJECTIVE
  This trial assessed the short-term efficacy and tolerability of adding a thiazolidinedione (rosiglitazone [ROS]) to existing sulfonylurea (SU) therapy (glibenclamide) compared with switching to combination treatment with a premixed insulin (biphasic insulin aspart 30 [BIAsp 30], a rapid-acting insulin analog) and the thiazolidinedione in a select group of patients with type 2 DM whose metabolic control was inadequate with SU monotherapy.
  
  
  METHODS
  In this 6-week, multicenter, open-label, parallel-group trial, patients with type 2 DM whose BG level was not adequately controlled with glibenclamide monotherapy (glycosylated hemoglobin [HbA1c] 8%-13%) were randomized either to replace glibenclamide with BIAsp 30 (individually titrated dosages starting with 6-8 U BID) plus rosiglitazone (4 mg once daily) (BIAsp 30 + ROS group) or to add rosiglitazone (4 mg once daily) to their pretrial doses of glibenclamide (GLIB + ROS group). Patients measured their BG levels immediately before each of the 3 main meals, 90 minutes after the start of each meal, and at bedtime, and mean BG levels were calculated at weeks 0 (baseline), 1, 2, 4, 6, and at 2-week follow-up (week 8). The primary end point was change in mean daily BG level during treatment. Secondary end points included preprandial, postprandial, and bedtime BG levels, serum fructosamine level HbA, and fasting BG level, which were measured at each study visit. Tolerability was assessed using hematologic and biochemical parameters, vital signs, and physical examination.
  
  
  RESULTS
  Forty-nine patients (32 men, 17 women; mean [SD] age, 59.1 [8.9] years; mean [SD] body mass index, 27.7 [3.7] kg/m2) participated in the study. A significant difference was found between treatments in the change in mean daily BG level from baseline to week 6 (P=0.01). After the 6-week treatment period, change in mean serum fructosamine level was significantly greater for BIAsp 30 + ROS compared with GLIB + ROS (P=0.02). HbA1c decreased in both treatment groups from baseline to study end, but the difference between groups was nonsignificant. The changes in fasting BG from baseline to study end also were nonsignificant between groups. Both combinations were well tolerated.
  
  
  CONCLUSIONS
  This short-term study in patients with type 2 DM whose BG level was poorly controlled with glibenclamide monotherapy suggests that switching to a combination of BIAsp 30 + ROS was efficacious and well tolerated and provided an alternative to adding rosiglitazone to existing glibenclamide treatment. The study also suggests that BIAsp 30 may be associated with greater improvements in short-term metabolic control.
authors.affiliation: Hadassah Ein Karem Medical Center, Jerusalem, Israel. ntv502@netvision.net.il
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Ulrik
authors.initials: U
authors.lastname: Mouritzen
authors.forename: Julius
authors.initials: J
authors.lastname: Vaz
authors.forename: Tommy
authors.initials: T
authors.lastname: Hershkovitz
authors.forename: Julio
authors.initials: J
authors.lastname: Wainstein
authors.forename: Ilana
authors.initials: I
authors.lastname: Harman-Boehm
mesh_terms: D000328:Adult; D000368:Aged; D061265:Biphasic Insulins; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D019270:Fructosamine / Q000097:blood; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D061267:Insulin Aspart; D007336:Insulin, Isophane; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D061265:Biphasic Insulins; D001786:Blood Glucose; D019270:Fructosamine; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D007336:Insulin, Isophane; D000077154:Rosiglitazone; D045162:Thiazolidinediones; C557564:insulin aspart, insulin aspart protamine drug combination 30:70