Pharmacokinetics and pharmacodynamics of glyburide/metformin tablets (Glucovance) versus equivalent doses of glyburide and metformin in patients with type 2 diabetes

Clin Pharmacokinet. 2002;41(15):1301-9. doi: 10.2165/00003088-200241150-00004.


Objective: To compare the effects of two different formulations of glibenclamide (glyburide) combined with metformin on postprandial glucose excursions, and to assess their pharmacokinetics. The formulations were a combination glibenclamide/metformin tablet (Glucovance; controlled-particle-size glibenclamide and metformin) versus glibenclamide (Micronase) and metformin (Glucophage) coadministered separately.

Design: A randomised, double-blind, two-way crossover study in which patients with type 2 diabetes received either glibenclamide/metformin 2.5/500mg tablets or glibenclamide 2.5mg with metformin 500mg twice daily for 14 days. After a 2-week washout, patients were crossed over to the other treatment for 14 days. Patients consumed standardised meals on the days when pharmacokinetic and pharmacodynamic evaluations were performed.

Participants: Forty patients with type 2 diabetes were enrolled; 37 were randomised (18 men, 19 women) and 35 completed the study. Mean age was 58 years; mean body mass index was 31 kg/m(2). The baseline glycated haemoglobin (HbA(1c)) was 9.3% for both treatment groups.

Main outcome measure: Two-hour postprandial glucose excursion (PPGE) was used to assess postprandial glucose dynamics.

Results: Treatment with glibenclamide/metformin resulted in a significantly smaller mean PPGE than was attained by treatment with glibenclamide plus metformin, according to measurements taken after the day 14 afternoon standardised meal (89.5 vs 117.4 mg/dl, p = 0.011). The mean glibenclamide peak concentration (C(max)) was significantly greater (approximately 16%) after glibenclamide/metformin treatment on both days 1 and 14. Glibenclamide/metformin treatment was associated with a 2-fold greater area under the concentration-time curve to 3 hours for glibenclamide (AUC(3)) [p < 0.001], although the AUC over the administration interval was equivalent for both formulations.

Conclusion: In patients with type 2 diabetes, glibenclamide/metformin resulted in lower PPGE, suggesting that the higher glibenclamide AUC(3) observed with this formulation may contribute to better postprandial glycaemic control than is attained by glibenclamide plus metformin separately.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Blood Glucose
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Glyburide / administration & dosage
  • Glyburide / pharmacokinetics*
  • Glyburide / therapeutic use*
  • Half-Life
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / pharmacokinetics*
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Postprandial Period
  • Tablets


  • Blood Glucose
  • Drug Combinations
  • Hypoglycemic Agents
  • Tablets
  • Glyburide