title: Optimizing insulin secretagogue therapy in patients with type 2 diabetes: a randomized double-blind study with repaglinide.
abstract: OBJECTIVE
  Repaglinide, a novel antidiabetic agent that has a rapid onset and short duration of action, was developed for mealtime dosing. The purpose of this pharmacodynamic study was to validate a prandial regimen of repaglinide by comparing meal-related dosing with a regimen in which the same total daily dose was divided into only two doses at morning and evening meals.
  
  
  METHODS
  The study was a double-blind, randomized, parallel-group trial in 19 antidiabetic agent-naive subjects with type 2 diabetes (mean age 58 years, known duration of diabetes 3.5 years, HbA(1c) 7.3%, and BMI 32 kg/m(2)). Patients were randomly assigned to receive repaglinide either before each of the three main meals or before breakfast and before the evening meal. Patients in both groups received the same total daily dose of repaglinide. Twenty-four hour profiles of blood glucose, plasma insulin, and plasma C-peptide concentrations were measured at baseline and after 4 weeks of treatment.
  
  
  RESULTS
  Repaglinide increased postprandial insulin levels and markedly reduced postprandial glucose levels relative to baseline in both groups. Significant reductions were also recorded in fasting blood glucose and HbA(1c) levels. The repaglinide regimen, in which a dose was taken before each main meal, was more effective in improving glycemic control (including postprandial glucose and HbA(1c) levels) than the same total dose of repaglinide divided into morning and evening mealtime doses.
  
  
  CONCLUSIONS
  These data support the strategy of mealtime dosing with repaglinide. The improvements in glycemic control observed in these patients are encouraging. In addition to classic parameters of glycemic control, improvements in postprandial glucose excursions may prove to be important because postprandial hyperglycemia has been suggested to be an independent risk factor for cardiovascular disease in diabetes.
authors.affiliation: Department of Endocrinology and Diabetes, University Hospital of Aarhus, DK-8000 Aarhus C, Denmark. ole.schmitz@iekf.au.dk
authors.forename: Ole
authors.initials: O
authors.lastname: Schmitz
authors.forename: Sten
authors.initials: S
authors.lastname: Lund
authors.forename: Per Heden
authors.initials: PH
authors.lastname: Andersen
authors.forename: Morten
authors.initials: M
authors.lastname: Jønler
authors.forename: Nils
authors.initials: N
authors.lastname: Pørksen
mesh_terms: D001786:Blood Glucose; D002219:Carbamates / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004435:Eating; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D019518:Postprandial Period
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D007328:Insulin; D010880:Piperidines; C072379:repaglinide