Aim: To compare the efficacy, safety and tolerability of a fixed combination glyburide/metformin preparation with those of glyburide or metformin alone in patients with type 2 diabetes inadequately controlled by sulphonylurea, diet and exercise.
Methods: In this 16-week, randomized, double-blind, parallel group study, 639 patients with inadequate glycaemic control on at least half-maximal dose of sulphonylurea were randomly assigned to: glyburide 10 mg b.i.d. (n = 164); metformin 500 mg (n = 153); glyburide/metformin 2.5 mg/500 mg (n = 160); or glyburide/metformin 5 mg/500 mg (n = 162). Titration was allowed to maximum doses of 2000 mg for metformin or 10 mg/2000 mg and 20 mg/2000 mg for glyburide/metformin 2.5 mg/500 mg and 5 mg/500 mg respectively. The primary outcome measure was HbA1c level after 16 weeks; secondary end-points included fasting and 2-h post-prandial plasma glucose. Adverse events (AEs) were recorded and summarized by treatment group.
Results: Both strengths of glyburide/metformin equally reduced mean HbA1c by 1.7% more than did glyburide alone (p < 0.001), and by 1.9% more than did metformin alone (p < 0.001). Final mean fasting plasma glucose concentrations were also lower in both glyburide/metformin groups than in the glyburide (-2.8 mmol/l, -51.3 mg/dl; p < 0.001) and metformin groups (-3.6 mmol/l, -64.2 mg/dl; p < 0.001). Safety and tolerability were similar across all treatment groups, except for a higher incidence of gastrointestinal AEs in the metformin monotherapy group, and more patients reporting mild or moderate symptoms of hypoglycaemia while taking glyburide/metformin.
Conclusions: Both glyburide/metformin tablet strengths produced, with equal efficacy, significantly better glycaemic control than monotherapy with either agent. These data also confirm that glycaemic efficacy does not require maximal sulphonylurea doses in combination with metformin.