ObjectiveTo 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.DesignA 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.ParticipantsForty 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 measureTwo-hour postprandial glucose excursion (PPGE) was used to assess postprandial glucose dynamics.ResultsTreatment 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.ConclusionIn patients with type 2 diabetes, glibenclamide/metformin resulted in lower PPGE, suggesting that the higher glibenclamide AUC3observed with this formulation may contribute to better postprandial glycaemic control than is attained by glibenclamide plus metformin separately.