title: Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin.
abstract: OBJECTIVE
  Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus.
  
  
  METHODS
  We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run-in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7.5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean +/- standard deviation), 300 +/- 60, 12.5 +/- 2.5, and 2500 +/- 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post-prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA(1c)), fasting (FPI) and post-prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), apolipoprotein A-I (Apo A-I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run-in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups.
  
  
  CONCLUSIONS
  Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA(1c) (P < 0.01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0.01 vs. baseline), PPG (P < 0.01 vs. baseline), and on HOMA index (P < 0.05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA(1c) (P < 0.05 vs. baseline), FPG (P < 0.01 vs. baseline), PPG (P < 0.05 vs. baseline), and HOMA index (P < 0.05 vs. baseline). No significant change was observed in TC, LDL-C, HDL-C, Tg, Apo A-I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin-resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control.
  
  
  CONCLUSIONS
  Nateglinide improved glycemic control better than glibenclamide in combination with metformin.
authors.affiliation: Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy. giuseppe.derosa@uni.pv.it
authors.forename: G
authors.initials: G
authors.lastname: Derosa
authors.forename: A
authors.initials: A
authors.lastname: D'Angelo
authors.forename: E
authors.initials: E
authors.lastname: Fogari
authors.forename: S
authors.initials: S
authors.lastname: Salvadeo
authors.forename: A
authors.initials: A
authors.lastname: Gravina
authors.forename: I
authors.initials: I
authors.lastname: Ferrari
authors.forename: A F G
authors.initials: AF
authors.lastname: Cicero
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005905:Glyburide / Q000494:pharmacology* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D003510:Cyclohexanes; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D008687:Metformin; D000077715:Nateglinide; D010649:Phenylalanine