In a multicenter, randomized, double-blind, active-controlled, dose-ranging, parallel group study conducted in patients type 2 diabetes mellitus, GLUMETZA 1,500 mg once daily, GLUMETZA 1,500 per day in divided doses (500 mg in the morning and 1,000 mg in the evening), and GLUMETZA 2,000 mg once daily were compared to immediate-release metformin HCl tablets 1,500 mg per day in divided doses (500 mg in the morning and 1,000 mg in the evening). This study included patients (n=338) who were newly diagnosed with diabetes, patients treated only with diet and exercise, patients treated with a single antidiabetic medication (sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, or meglitinides), and patients (n=368) receiving metformin HCl tablets up to 1,500 mg/day plus a sulfonylurea at a dose equal to or less than one-half the maximum dose. Patients who were enrolled on monotherapy or combination antidiabetic therapy underwent a 6-week washout. Patients randomized to GLUMETZA began titration from 1,000 mg/day up to their assigned treatment dose over 3 weeks. Patients randomized to immediate-release metformin initiated 500 mg twice daily for 1 week followed by 500 mg with breakfast and 1,000 mg with dinner for the second week. The 3-week treatment period was followed by an additional 21-week period at the randomized dose. The results are presented in Table 5.

Mean baseline body weight was 88.2 kg, 90.5 kg, 87.7 kg and 88.7 kg in the GLUMETZA 1,500 mg once daily, GLUMETZA 1,500 mg in divided doses, GLUMETZA 2,000 mg once daily and metformin HCl tablets 1,500 mg in divided doses arms, respectively. Mean change in body weight from baseline to week 24 was -0.9 kg, -0.7 kg, -1.1 kg, and -0.9 kg in the GLUMETZA 1,500 mg once daily, GLUMETZA 1,500 mg in divided doses, GLUMETZA 2,000 mg once daily and metformin HCl tablets 1,500 mg in divided doses arms, respectively.

A double-blind, randomized, placebo-controlled (glyburide add-on) multicenter study enrolled patients with type 2 diabetes mellitus who were newly diagnosed or treated with diet and exercise (n=144), or who were receiving monotherapy with metformin, sulfonylureas, alpha-glucosidase inhibitors, thiazolidinediones, or meglitinides, or treated with combination therapy consisting of metformin HCl/glyburide at doses up to 1,000 mg metformin + 10 mg glyburide per day (or equivalent doses of glipizide or glimepiride up to half the maximum therapeutic dose) (n=431). All patients were stabilized on glyburide for a 6-week run-in period, and then randomized to 1 of 4 treatments: placebo + glyburide (glyburide alone); GLUMETZA 1,500 mg once a day + glyburide, GLUMETZA 2,000 mg once a day + glyburide, or GLUMETZA 1,000 mg twice a day + glyburide. A 3-week GLUMETZA titration period was followed by a 21-week maintenance treatment period. Use of insulin and oral hypoglycemic agents other than the study drugs were prohibited. The results are presented in Table 6.

Mean baseline body weight was 89.4 kg, 103.7 kg, 102.9 kg and 95.6 kg in the GLUMETZA 1,500 mg once daily, GLUMETZA 1,500 mg in divided doses, GLUMETZA 2,000 mg once daily and metformin HCl tablets 1,500 mg in divided doses arms, respectively. Mean change in body weight from baseline to week 24 was 0.3 kg, 0.1 kg, 0 kg, and 0.7 kg in the GLUMETZA 1,500 mg once daily, GLUMETZA 1,500 mg in divided doses, GLUMETZA 2,000 mg once daily and metformin HCl tablets 1,500 mg in divided doses arms, respectively.