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) with 19% less insulin versus baseline (reduction of 23.68 ± 30.22 versus an increase of 0.43 ± 25.20 units for metformin plus insulin and placebo plus insulin, p<0.01). In addition, this study demonstrated that the combination of metformin plus insulin resulted in reduction in body weight of 3.11 ± 4.30 lbs, compared to an increase of 1.30 ± 6.08 lbs for placebo plus insulin, p=0.01.
Table 3: Mean±SE Changes from Baseline to Final Visit in HbA1c, Fasting Plasma Glucose and Body Weight for the GLUMETZA and Metformin IR Treatment Groups (First 24-Week Study) Parameter GLUMETZA Metformin IR
1500 mg AM/PM
(n = 174)
1500 mg QD
(n = 178) 1500 mg AM/PM
(n = 182) 2000 mg QD
(n = 172)
HbA1c (%)
n 169 175 159 170
Baseline 8.22 ± 0.25 8.50 ± 0.24 8.26 ± 0.24 8.70 ± 0.25
Mean Change ± SE at Final Visit -0.73 ± 0.12 -0.74 ± 0.12 -1.06 ± 0.12 -0.70 ± 0.12
Mean Difference ± SE from Metformin IR -0.03 ± 0.12 -0.04 ± 0.12 -0.36 ± 0.12 N/A
98.4% CI for Difference (-0.32, 0.26) (-0.33, 0.25) (-0.65, -0.06)
Fasting Plasma Glucose (mg/dL)
n 175 179 170 172
Baseline 190.0 ± 9.9 192.5 ± 9.9 183.9 ± 9.9 196.5 ± 11.2
Mean Cha
