###  Patients with Inadequate Glycemic Control on Diet and Exercise Alone

In a 20-week, double-blind, multicenter U.S. clinical trial, a total of 806 drug-naive patients with type 2 diabetes, whose hyperglycemia was not adequately controlled with diet and exercise alone (baseline fasting plasma glucose [FPG] <240 mg/dL, baseline hemoglobin A1c [HbA1c] between 7% and 11%), were randomized to receive initial therapy with placebo, 2.5 mg glyburide, 500 mg metformin, Glyburide and Metformin Hydrochloride Tablets 1.25 mg/250 mg, or Glyburide and Metformin Hydrochloride Tablets 2.5 mg/500 mg. After four weeks, the dose was progressively increased (up to the eight-week visit) to a maximum of four tablets daily as needed to reach a target FPG of 126 mg/dL. Trial data at 20 weeks are summarized in Table 2. 

Treatment with Glyburide and Metformin Hydrochloride Tablets resulted in significantly greater reduction in HbA1c and postprandial plasma glucose (PPG) compared to glyburide, metformin, or placebo. Also, Glyburide and Metformin Hydrochloride Tablets therapy resulted in greater reduction in FPG compared to glyburide, metformin, or placebo, but the differences from glyburide and metformin did not reach statistical significance. 

Changes in the lipid profile associated with Glyburide and Metformin Hydrochloride Tablets treatment were similar to those seen with glyburide, metformin, and placebo. 

The double-blind, placebo-controlled trial described above restricted enrollment to patients with HbA1c<11% or FPG <240 mg/dL. Screened patients ineligible for the first trial because of HbA1c and/or FPG exceeding these limits were treated directly with Glyburide and Metformin Hydrochloride Tablets 2.5 mg/500 mg in an open-label, uncontrolled protocol. In this study, three out of 173 patients (1.7%) discontinued because of inadequate therapeutic response. Across the group of 144 patients who completed 26 weeks of treatment, mean HbA1c was reduced from a baseline of 10.6% to 7.1%. The mean baseline FPG was 283 mg/dL and was reduced to 164 and 161 mg/dL after 2 and 26 weeks, respectively. The mean final titrated dose of Glyburide and Metformin Hydrochloride Tablets was 7.85 mg/1569 mg (equivalent to approximately three Glyburide and Metformin Hydrochloride Tablets 2.5 mg/500 mg per day). 

###  Patients with Inadequate Glycemic Control on Sulfonylurea Alone 

In a 16-week, double-blind, active-controlled U.S. clinical trial, a total of 639 patients with type 2 diabetes not adequately controlled (mean baseline HbA1c 9.5%, mean baseline FPG 213 mg/dL) while being treated with at least one-half the maximum dose of a sulfonylurea (e.g., glyburide 10 mg, glipizide 20 mg) were randomized to receive glyburide (fixed dose, 20 mg), metformin (500 mg), Glyburide and Metformin Hydrochloride Tablets 2.5 mg/500 mg, or Glyburide and Metformin Hydrochloride Tablets 5 mg/500 mg. The doses of metformin and Glyburide and Metformin Hydrochloride Tablets were titrated to a maximum of four tablets daily as needed to achieve FPG <140 mg/dL. Trial data at 16 weeks are summarized in Table 3. 

After 16 weeks, there was no significant change in the mean HbA1c in patients randomized to glyburide or to metformin therapy. Treatment with Glyburide and Metformin Hydrochloride Tablets at doses up to 20 mg/2000 mg per day resulted in significant lowering of HbA1c, FPG, and PPG from baseline compared to glyburide or metformin alone. 

###  Addition of Thiazolidinediones to Glyburide and Metformin Hydrochloride Tablets Therapy 

In a 24-week, double-blind, multicenter U.S. clinical trial, patients with type 2 diabetes not adequately controlled on current oral antihyperglycemic therapy (either monotherapy or combination therapy) were first switched to open label Glyburide and Metformin Hydrochloride Tablets 2.5 mg/500 mg and titrated to a maximum daily dose of 10 mg/2000 mg. A total of 365 patients inadequately controlled (HbA1c >7.0% and ≤10%) after 10 to 12 weeks of a daily Glyburide and Metformin Hydrochloride Tablets dose of at least 7.5 mg/1500 mg were randomized to receive add-on therapy with rosiglitazone 4 mg or placebo once daily. After eight weeks, the rosiglitazone dose was increased to a maximum of 8 mg daily as needed to reach a target mean daily glucose of 126 mg/dL or HbA1c <7%. Trial data at 24 weeks or at the last prior visit are summarized in Table 4. 

For patients who did not achieve adequate glycemic control on Glyburide and Metformin Hydrochloride Tablets, the addition of rosiglitazone, compared to placebo, resulted in significant lowering of HbA1c and FPG.