title: Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.
abstract: OBJECTIVE
  To evaluate whether simultaneous initial treatment of both insulin resistance and impaired beta-cell insulin secretion with glyburide/metformin tablets is superior to monotherapy with each component agent.
  
  
  METHODS
  In this randomized, parallel-group, placebo-controlled, multicentre study, 806 patients with type 2 diabetes (mean duration, 3 years) who had failed diet and exercise were randomly assigned to 4 weeks of therapy with placebo, glyburide 2.5 mg, metformin 500 mg, glyburide/metformin 1.25/250 mg, or glyburide/metformin 2.5/500 mg once daily. Doses were then titrated over 8 weeks based on glycaemic response. The primary outcome measure was change from baseline in mean HbA1c after 20 weeks. Changes in fasting plasma glucose, lipids and body weight were also assessed along with 2-h postprandial glucose and insulin values after a standardized meal.
  
  
  RESULTS
  At week 20, patients taking glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in HbA1c levels (-1.48% and -1.53% respectively) compared with placebo (-0.21%; both p < 0.001), glyburide (-1.24%; p = 0.016 and p = 0.004 respectively) or metformin (-1.03%; both p < 0.001). Fasting plasma glucose concentrations were reduced more in both glyburide/metformin groups compared with placebo and metformin (p < 0.001); patients in both combination therapy groups also had significantly lower postprandial glucose concentrations compared with placebo, glyburide and metformin.
  
  
  CONCLUSIONS
  Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy. The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes.
authors.affiliation: Baylor College of Medicine and The Methodist Hospital, Houston, Texas 77030, USA. agarber@bcm.tmc.edu
authors.forename: A J
authors.initials: AJ
authors.lastname: Garber
authors.forename: J
authors.initials: J
authors.lastname: Larsen
authors.forename: S H
authors.initials: SH
authors.lastname: Schneider
authors.forename: B A
authors.initials: BA
authors.lastname: Piper
authors.forename: D
authors.initials: D
authors.lastname: Henry
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D010919:Placebos; D019518:Postprandial Period; D044469:Racial Groups; D012449:Safety; D014481:United States
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010919:Placebos; D008687:Metformin; D005905:Glyburide