Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin

G. Derosa, A. D'Angelo, E. Fogari, S. Salvadeo, A. Gravina, I. Ferrari, A. F G Cicero

Research output: Contribution to journalArticlepeer-review


Background and 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 (HbA1c), 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. Results and discussion: Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA1c (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 HbA1c (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. Conclusion: Nateglinide improved glycemic control better than glibenclamide in combination with metformin.

Original languageEnglish
Pages (from-to)13-23
Number of pages11
JournalJournal of Clinical Pharmacy and Therapeutics
Issue number1
Publication statusPublished - Feb 2009


  • Glibenclamide
  • Insulin-resistance
  • Metformin
  • Nateglinide
  • Oral antidiabetic agents

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

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