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

In a 24 week, double-blind, active-controlled, multicenter international clinical trial, patients with type 2 diabetes, whose hyperglycemia was not adequately controlled with diet and exercise alone (hemoglobin A1c [HbA1c] > 7.5% and ≤ 12% and fasting plasma glucose [FPG] < 300 mg/dL) were randomized to receive initial therapy with glipizide 5 mg, metformin 500 mg, glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, or glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg. After 2 weeks, the dose was progressively increased (up to the 12 week visit) to a maximum of 4 tablets daily in divided doses as needed to reach a target mean daily glucose (MDG) of ≤ 130 mg/dL. Trial data at 24 weeks are summarized in Table 2.

After 24 weeks, treatment with glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg and 2.5 mg/500 mg resulted in significantly greater reduction in HbA1c compared to glipizide and metformin therapy. Also, glipizide and metformin hydrochloride tablet, 2.5 mg/250 mg therapy resulted in significant reductions in FPG versus metformin therapy.

Increases above fasting glucose and insulin levels were determined at baseline and final study visits by measurement of plasma glucose and insulin for 3 hours following a standard mixed liquid meal. Treatment with glipizide and metformin hydrochloride tablets lowered the 3 hour postprandial glucose AUC, compared to baseline, to a significantly greater extent than did the glipizide and the metformin therapies. Compared to baseline, glipizide and metformin hydrochloride tablets enhanced the postprandial insulin response, but did not significantly affect fasting insulin levels.

There were no clinically meaningful differences in changes from baseline for all lipid parameters between glipizide and metformin hydrochloride tablet therapy and either metformin therapy or glipizide therapy. The adjusted mean changes from baseline in body weight were: glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, -0.4 kg; glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg, -0.5 kg; glipizide, -0.2 kg; and metformin, -1.9 kg. Weight loss was greater with metformin than with glipizide and metformin hydrochloride tablets.

### Patients With Inadequate Glycemic Control on Sulfonylurea Monotherapy 

In an 18 week, double-blind, active-controlled U.S. clinical trial, a total of 247 patients with type 2 diabetes not adequately controlled (HbA1c ≥ 7.5% and ≤ 12% and FPG < 300 mg/dL) while being treated with at least one-half the maximum labeled dose of a sulfonylurea (e.g., glyburide 10 mg, glipizide 20 mg) were randomized to receive glipizide (fixed dose, 30 mg), metformin (500 mg), or glipizide and metformin hydrochloride tablets, 5 mg/500 mg. The doses of metformin and glipizide and metformin hydrochloride tablets were titrated (up to the 8 week visit) to a maximum of 4 tablets daily as needed to achieve MDG ≤ 130 mg/dL. Trial data at 18 weeks are summarized in Table 3.

After 18 weeks, treatment with glipizide and metformin hydrochloride tablets at doses up to 20 mg/2000 mg per day resulted in significantly lower mean final HbA1c and significantly greater mean reductions in FPG compared to glipizide and metformin therapy. Treatment with glipizide and metformin hydrochloride tablets lowered the 3 hour postprandial glucose AUC, compared to baseline, to a significantly greater extent than did the glipizide and the metformin therapies. Glipizide and metformin hydrochloride tablets did not significantly affect fasting insulin levels.

There were no clinically meaningful differences in changes from baseline for all lipid parameters between glipizide and metformin hydrochloride tablet therapy and either metformin therapy or glipizide therapy. The adjusted mean changes from baseline in body weight were: glipizide and metformin hydrochloride tablets, 5 mg/500 mg, -0.3 kg; glipizide, -0.4 kg; and metformin, -2.7 kg. Weight loss was greater with metformin than with glipizide and metformin hydrochloride tablets.