, active-controlled, dose-ranging, parallel group study GLUMETZA 1500 mg once a day, GLUMETZA 1500 per day in divided doses (500 mg in the morning and 1000 mg in the evening), and GLUMETZA 2000 mg once a day were compared to immediate release metformin 1500 mg per day in divided doses (500 mg in the morning and 1000 mg in the evening). (See Table 3) Newly diagnosed patients, diet-and-exercise-treated (diet/exercise) patients, patients who received combination therapy consisting of metformin up to 1500 mg/day plus a sulfonylurea at a dose equal to or less than one-half the maximum dose allowed (following a 6-week washout), or patients on monotherapy with an antihyperglycemic agent (following a 6-week washout) were randomized to treatment and began titration from 1000 mg/day up to their assigned treatment dose over 3 weeks. Metformin IR treatment was initiated as 500 mg BID for 1 week followed by 500 mg with breakfast and 1000 mg with dinner for the second week. The 3-week treatment period was followed by an additional 21-week period at the randomized dose. Each of the GLUMETZA regimens were at least as effective as immediate release metformin in all measures of glycemic control. Additionally, once daily dosing was as effective as the commonly prescribed twice daily dosing of the immediate release metformin formulation.
In a double-blind, randomized, placebo-controlled (glyburide add-on) multicenter study, patients with type 2 diabetes mellitus who were newly diagnosed or treated with diet and exercise, or who were receiving monotherapy with metformin, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, or meglinitides, or treated with combination therapy consisting of metformin/glyburide at doses up to 1000 mg metformin + 10 mg glyburide per day (or equivalent doses of glipizide or glimepiride up to half the maximum therapeutic dose) were enrolled. They were stabilized on glyburide for a 6-week period, and then randomized to 1 of 4 treatments: placebo + glyburide (glyburide alone); GLUMETZA 1500 mg once a day + glyburide, GLUMETZA 2000 mg once a day + glyburide, or GLUMETZA 1000 mg twice a day + glyburide. A 3-week GLUMETZA titration phase was followed by a 21-week maintenance treatment phase. The difference in the change from Baseline in HbA levels between the combined M-ER+ SU (sulfonylurea) groups and the SU only group was statistically significant (p<0.001). The changes in glycemic control across the three GLUMETZA+glyburide groups were comparable. (See Table 4)
A 24-week, double-blind, placebo-controlled study of immediate release metformin plus insulin versus insulin plus placebo was conducted in patients with type 2 diabetes who failed to achieve adequate glycemic control on insulin alone. Patients randomized to receive metformin plus insulin achieved a reduction in HbA of 2.10%, compared to a 1.56% reduction in HbA achieved by insulin plus placebo. The improvement in glycemic control was achieved at the final study visit with 16% less insulin, 93.0 U/day vs. 110.6 U/day, metformin plus insulin versus insulin plus placebo, respectively, p=0.04. A second double-blind, placebo-controlled study (n=51), with 16 weeks of randomized treatment, demonstrated that in patients with type 2 diabetes controlled on insulin for 8 weeks with an average HbA of 7.46 ± 0.97%, the addition of metformin maintained similar glycemic control (HbA 7.15 ± 0.61 versus 6.97 ± 0.62 for metformin plus insulin and placebo plus insulin, respectively) wit
