Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes

Objective: To evaluate whether simultaneous initial treatment of both insulin resistance and impaired β-cell insulin secretion with glyburide/metformin tablets is superior to monotherapy with each component agent. Research Design and Methods: In this randomized, parallel-group, placebo-controlled, multicentre study, 806 patients with type 2 diabetes (mean duration, 3 years) who had failed diet and exercise were randomly assigned to 4 weeks of therapy with placebo, glyburide 2.5 mg, metformin 500 mg, glyburide/metformin 1.25/250 mg, or glyburide/metformin 2.5/500 mg once daily. Doses were then titrated over 8 weeks based on glycaemic response. The primary outcome measure was change from baseline in mean HbA_1c after 20 weeks. Changes in fasting plasma glucose, lipids and body weight were also assessed along with 2-h postprandial glucose and insulin values after a standardized meal. Results: At week 20, patients taking glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in HbA_1c levels (-1.48% and -1.53% respectively) compared with placebo (-0.21%; both p < 0.001), glyburide (-1.24%; p = 0.016 and p = 0.004 respectively) or metformin (-1.03%; both p < 0.001). Fasting plasma glucose concentrations were reduced more in both glyburide/metformin groups compared with placebo and metformin (p < 0.001); patients in both combination therapy groups also had significantly lower postprandial glucose concentrations compared with placebo, glyburide and metformin. Conclusions: Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy. The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes.