title: Efficacy and safety of biphasic insulin aspart 30 combined with pioglitazone in type 2 diabetes poorly controlled on glibenclamide (glyburide) monotherapy or combination therapy: an 18-week, randomized, open-label study.
abstract: BACKGROUND
  Few large randomized controlled trials have assessed the value of adding insulin to an oral antidiabetic drug regimen.
  
  
  OBJECTIVE
  This trial compared the efficacy and safety of biphasic insulin aspart 30/70 (BIAsp 30) plus pioglitazone (n = 93), glibenclamide (glyburide) plus pioglitazone (n = 91), or BIAsp 30 monotherapy (n = 97).
  
  
  METHODS
  This 18-week, multinational, multicenter, randomized, open-label, parallel-group trial involved 281 patients with type 2 diabetes (60% male; mean age, 56 years; mean body mass index, 29.5 kg/m2) with inadequate glycemic control (mean glycosylated hemoglobin [HbA(1c)], 9.5%; range, 7.4%-14.7%) on glibenclamide monotherapy or combination therapy. The primary objective was to compare end-of-trial HbA(1c) among the 3 treatment groups. Fasting and mean 7- and 8-point blood glucose profiles, blood lipid levels, plasminogen activator inhibitor levels, adverse events, and hypoglycemia frequency were also compared. Patients using BIAsp 30 (alone or with pioglitazone) were injected twice daily (immediately before breakfast and dinner). Pioglitazone (30 mg/d) and glibenclamide (5-15 mg/d) were taken orally once daily with or immediately after breakfast.
  
  
  RESULTS
  At the end of the trial, HbA(1c) was significantly lower for the BIAsp 30 plus pioglitazone group than for the glibenclamide plus pioglitazone group (mean [SD], -0.64% [0.23%]; P = 0.005) and the BIAsp 30 monotherapy group (-0.60% [0.22%]; P = 0.008). Mean (SD) fasting blood glucose (before breakfast) was significantly lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone (153 [45] mg/dL vs 169 [65] mg/dL, respectively; P = 0.012). Each time point on the 8-point blood glucose profile was lower for BIAsp 30 plus pioglitazone than for glibenclamide plus pioglitazone (P < 0.001 to P < 0.05). No major hypoglycemic episodes were reported, and the absolute rate of hypoglycemic events was low (<1 event/patient-week) in the BIAsp-only group. Edema was reported in < or =9% of patients in each treatment group, but no occurrence was classified as serious. Weight gain (mean, 4.0 kg) was more common in the BIAsp plus pioglitazone group (8%); however, this was consistent with improved glycemic control and is similar to that reported in other pioglitazone trials.
  
  
  CONCLUSIONS
  BIAsp 30 plus pioglitazone provided an efficacious and well-tolerated treatment alternative to glibenclamide plus pioglitazone or BIAsp 30 alone in this population of patients who previously were not well controlled on glibenclamide monotherapy or combination therapy.
authors.affiliation: Diabetes Unit, Hadassah Hebrew University Hospital, Jerusalem, Israel. ntv502@netvision.net.il
authors.forename: Itamar
authors.initials: I
authors.lastname: Raz
authors.forename: Stephen
authors.initials: S
authors.lastname: Stranks
authors.forename: Robert
authors.initials: R
authors.lastname: Filipczak
authors.forename: Pankaj
authors.initials: P
authors.lastname: Joshi
authors.forename: Benedikte
authors.initials: B
authors.lastname: Lertoft
authors.forename: Jacob
authors.initials: J
authors.lastname: Rastam
authors.forename: Chun-Chung
authors.initials: CC
authors.lastname: Chow
authors.forename: Joseph
authors.initials: J
authors.lastname: Shaban
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000008:administration & dosage / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use*; D008297:Male; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D045162:Thiazolidinediones; D014280:Triglycerides