title: Efficacy and safety of combination therapy: repaglinide plus metformin versus nateglinide plus metformin.
abstract: OBJECTIVE
  An open-label, parallel-group, randomized, multicenter trial was conducted to compare efficacy and safety of repaglinide versus nateglinide, when used in a combination regimen with metformin for treatment of type 2 diabetes.
  
  
  METHODS
  Enrolled patients (n = 192) had HbA(1c) >7% and < or =12% during previous treatment with a sulfonylurea, metformin, or low-dose Glucovance (glyburide < or =2.5 mg, metformin < or =500 mg). After a 4-week metformin run-in therapy period (doses escalated to 1,000 mg b.i.d.), patients were randomized to addition of repaglinide (n = 96) (1 mg/meal, maximum 4 mg/meal) or nateglinide (n = 96) (120 mg/meal, reduced to 60 mg if needed) to the regimen for 16 weeks. Glucose, insulin, and glucagon were assessed after a liquid test meal at baseline and week 16.
  
  
  RESULTS
  Final HbA(1c) values were lower for repaglinide/metformin treatment than for nateglinide/metformin (7.1 vs. 7.5%). Repaglinide/metformin therapy showed significantly greater mean reductions of HbA(1c) (-1.28 vs. -0.67%; P < 0.001) and of fasting plasma glucose (FPG) (-39 vs. -21 mg/dl; P = 0.002). Self-monitoring of blood glucose profiles were significantly lower for repaglinide/metformin before breakfast, before lunch, and at 2:00 A.M. Changes in the area under the curve of postprandial glucose, insulin, or glucagon peaks after a test meal were not significantly different for the two treatment groups during this study. Median final doses were 5.0 mg/day for repaglinide and 360 mg/day for nateglinide. Safety assessments were comparable for the two regimens.
  
  
  CONCLUSIONS
  The addition of repaglinide to metformin therapy resulted in reductions of HbA(1c) and FPG values that were significantly greater than the reductions observed for addition of nateglinide.
authors.affiliation: Departemtn of Internal Medicine, Southwestern Medical Center, University of Texas, Dallas, Texas 75390-8858, USA. philip.raskin@utsouthwestern.edu
authors.forename: Philip
authors.initials: P
authors.lastname: Raskin
authors.forename: Leslie
authors.initials: L
authors.lastname: Klaff
authors.forename: Janet
authors.initials: J
authors.lastname: McGill
authors.forename: Stephen A
authors.initials: SA
authors.lastname: South
authors.forename: Priscilla
authors.initials: P
authors.lastname: Hollander
authors.forename: Naum
authors.initials: N
authors.lastname: Khutoryansky
authors.forename: Paula M
authors.initials: PM
authors.lastname: Hale
mesh_terms: D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000009:adverse effects / Q000627:therapeutic use*; D003510:Cyclohexanes / Q000009:adverse effects / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use*; D019518:Postprandial Period; D012449:Safety
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D000077715:Nateglinide; D010649:Phenylalanine; D010880:Piperidines; C072379:repaglinide