Durability of efficacy and long-term safety profile of glyburide/metformin tablets in patients with type 2 diabetes mellitus: An open-label extension study

Background: Intensive glycemic control substantially reduces the microvascular and macrovascular complications of type 2 diabetes mellitus, although less than half of patients with diabetes achieve the target glycosylated hemoglobin (HbA(1c)) value recommended by the American Diabetes Association. Because monotherapy with an oral agent does not address the multiple pathophysiologic defects of diabetes, use of combination therapy appears to be warranted. A previous 32-week, randomized, double-blind, placebo-controlled trial found that treatment with glyburide/metformin tablets was associated with greater reductions in HbA(1c) values compared with glyburide monotherapy, metformin monotherapy, and placebo. Objectives: This study evaluated the durability of efficacy and long-term safety profile of therapy with glyburide/metformin tablets over 52 weeks. Methods: Patients enrolled in this open-label extension study were drawn from 3 groups: those who completed the 32-week double-blind study, those who were discontinued from the double-blind study, and those who were ineligible for the double-blind study and were enrolled directly in the open-label extension study. Patients with an HbA(1c) of <9% received glyburide/metformin 1.25 mg/250 mg tablets BID, and those with an HbA(1c) of greater than or equal to9% received glyburide/metformin 2.5 mg/500 mg tablets BID. Primary efficacy variables included changes from baseline in HbA(1c) fasting plasma glucose (FPG), and body weight at week 52. Safety was assessed based on adverse-event data and the results of physical examinations and laboratory tests. Results: A total of 828 patients were enrolled in the study: 515 who completed the 32-week double-blind study, 138 who were discontinued from the double-blind study, and 175 who were directly enrolled. At week 52, the mean HbA(1c) value for the entire population had decreased from a baseline value of 8.73% to 7.04% (95% CI, -1.81 to -1.58). Patients who were enrolled directly had the poorest glycemic control at baseline and experienced the greatest reduction in HbA(1c) (-3.35%; 95% CI, -3.61 to -3.10). A reduction in mean FPG for the total population was observed as early as week 2, from 201 to 141 mg/dL (95% CI, -63.0 to -55.7). Symptoms of hypoglycemia occurred in 19.9% (165/828) of patients, although only one third of these patients had a documented finger-stick blood glucose value of less than or equal to50 mg/dL. Conclusions: In this 52-week, open-label extension study, glyburide/metformin tablets were well tolerated and effective in patients with type 2 diabetes. They provided rapid and sustainable reductions in HbA(1c) values and FPG concentrations.