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Pharmacokinetics and Pharmacodynamics of Glyburide/Metformin Tablets (Glucovance™) versus Equivalent Doses of Glyburide and Metformin in Patients with Type 2 Diabetes

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Abstract

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/m2. The baseline glycated haemoglobin (HbA1c) 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 (Cmax) was significantly greater (∼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 (AUC3) [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 AUC3 observed with this formulation may contribute to better postprandial glycaemic control than is attained by glibenclamide plus metformin separately.

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Notes

  1. Referred to as glyburide in the US.

  2. Use of tradenames is for product identification only and does not imply endorsement.

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Acknowledgements

Funding for the study was provided by the Bristol-Myers Squibb Company, and Drs Donahue and Turner are employed by the Bristol-Myers Squibb Company.

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Donahue, S.R., Turner, K.C. & Patel, S. Pharmacokinetics and Pharmacodynamics of Glyburide/Metformin Tablets (Glucovance™) versus Equivalent Doses of Glyburide and Metformin in Patients with Type 2 Diabetes. Clin Pharmacokinet 41, 1301–1309 (2002). https://doi.org/10.2165/00003088-200241150-00004

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  • DOI: https://doi.org/10.2165/00003088-200241150-00004

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