ha-glucosidase inhibitors, thiazolidinediones, or meglinitides, or treated with combination therapy consisting of metformin/glyburide at doses up to 1000mg metformin+ 10mg glyburide per day (or equivalent doses of glipizide or glimepiride up to half the maximum therapeutic dose) (n= 431) were enrolled. All patients were stabilized on glyburide for a 6-week run-in period, and then randomized to 1 of 4treatments: placebo+ glyburide (glyburide alone); GLUMETZA 1500mg once a day+ glyburide, GLUMETZA 2000mg once a day+ glyburide, or GLUMETZA 1000mg twice a day+ glyburide. A 3-week GLUMETZA titration phase was followed by a 21-week maintenance treatment phase. Use of insulin and oral hypoglycemic agents other than the study drugs were prohibited. The difference in the change from Baseline in HbA1c levels between the combined GLUMETZA+ glyburide groups and the glyburide only group was statistically significant at week24 (p<0.001). The changes in glycemic control across the three GLUMETZA+ glyburide groups were comparable.
Table 5: Mean±SE Changes from Baseline to Final Visit in HbA1c, Fasting Plasma Glucose and Body Weight for the GLUMETZA/Glyburide Groups and Placebo/Glyburide Treatment Group (Second 24-Week Study) Parameter GLUMETZA+ Glyburide* Placebo/
Glyburide*
(n= 144)
1500mg QD
(n= 144) 1000mg BID
(n= 141) 2000mg QD
(n= 146)
* - Glyburide was administered as 10mg at breakfast and 5mg at dinner.
HbA1c (%)
N 136 136 144 141
Baseline 7.9± 0.1 7.8± 0.1 7.7± 0.1 8.1± 0.1
Mean Change± SE at Final Visit -0.7± 0.1 -0.8± 0.1 -0.7± 0.1 -0.1± 0.1
Mean Difference± SE from Glyburide Alone -0.8± 0.1 -0.9± 0.1 -0.8± 0.1 N/A
95% CI for Difference (-1.0, -0.6) (-1.1, -0.7) (-1.0, -0.6)
p-value for pairwise comparison <0.001 <0.001 <0.001
Fasting Plasma Glucose (mg/dL)
N 143 141 145 144
Baseline 163± 5 163± 5 159± 5 164± 5
Mean Change± SE at Final Visit -14± 4 -16± 4 -9± 4 16± 4
Mean Difference± SE from Glyburide Alone -29.2± 4.9 -31.2± 40.9 -24.9± 4.9 N/A
95% CI for Difference (-39, -20) (-41, -22) (-35, -15)
p-value for pairwise comparison <0.001 <0.001 <0.001
Body Weight (kg)
N 143 141 146 144
Baseline 89.4± 11.2 103.7± 11.2 102.9± 11.2 95.6± 8.0
Mean Change± SE at Final Visit 0.3± 1.1 0.1± 1.1 0± 1.1 0.7± 1.0
Mean Difference± SE from Glyburide Alone -0.4± 0.5 -0.6± 0.5 -0.7± 0.5 N/A
95% CI for Difference (-1.5, 0.6) (-1.7, 0.4) (-1.8, 0.3)
p-value for pairwise comparison 0.410 0.230 0.156
A 24-week, double-blind, placebo-controlled trial of immediate release metformin plus insulin versus insulin plus placebo was conducted in patients with type2 diabetes who failed to achieve adequate glycemic control on insulin alone. Patients randomized to receive metformin plus insulin achieved a mean reduction in HbA1c of 2.10%, compared to a 1.56% reduction in HbA1c achieved by insulin plus placebo. The improvement in glycemic control was achieved at the final study visit with 16% less insulin, 93.0U/day vs. 110.6U/day, metformin plus insulin
