A comparison of preconstituted, fixed combinations of low-dose glyburide plus metformin versus high-dose glyburide alone in the treatment of type 2 diabetic patients

In the present study we assessed and compared the effectiveness and safety of preconstituted, fixed, combinations of low-dose glyburide plus metformin with higher dose glyburide monotherapy in patients with type 2 diabetes. T his randomized, double-blind, cross-over study comprised 40 patients. After a 30-day run-in period of dietary treatment, patients received combined gl yburide (5, 7.5 or 10 mg/day) and metformin (800, 1,200 or 1,600 mg/day) as preconstitued, fixed combinations, or glyburide alone (5, 10 or 15 mg/day) . The dose was increased stepwise so as to have 1 (T1), 2 (T2) and 3 (T3) m onths of treatment for any given regimen (6 months in total). After 2 weeks of washout (T4), the groups were then crossed over (T5, T6, T7 periods). B ody weight, fasting plasma glucose, HbA(1c), blood lactate, total cholester ol and HDL-cholesterol, and triglycerides were measured at the beginning an d end of T1 and T5, and end of T2, T3, T6 and T7; postprandial plasma gluco se, fasting and postprandial plasma insulin and C-peptide were evaluated at the beginning of T1 and T5, and end of T3 and T7. At these latter time poi nts additional assessments included routine clinical chemistry measurements , EGG, and ophthalmoscopic examination. Statistical analysis was performed by the paired Student's t-test and analysis of variance for cross-over stud ies. Thirty-three patients completed the study. Fasting plasma glucose, pos tprandial plasma glucose and HbA(1c) levels improved significantly during c ombined treatment with glyburide at lower doses plus metformin. This effect was achieved without any major change of insulin and C-peptide concentrati ons. Circulating lactate concentrations increased during the regimen includ ing metformin, but they remained well within the reference values for norma l subjects. Plasma total cholesterol and triglycerides levels remained subs tantially unchanged throughout the study, whereas HDL-cholesterol concentra tions increased slightly, but significantly, with glyburide plus metformin therapy. Routine clinical chemistry measurements, ECG and ophthalmoscopic e xaminations did not change during the study. These results demonstrate that improved metabolic control can be achieved with preconstituted, fixed comb inations of low-dose glyburide plus metformin in patients with type 2 diabe tes, compared to higher doses of the sulphonylurea alone.