Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including glipizide. Alternatively, glipizide may be effective in some patients who have not responded or have ceased to respond to other sulfonylureas.

Effects on Blood Glucose
The effectiveness of GLUCOTROL XL Extended Release Tablets in type 2 diabetes at doses from 5–60 mg once daily has been eva luated in 4 therapeutic clinical trials each with long-term open extensions involving a total of 598 patients. Once daily administration of 5, 10 and 20 mg produced statistically significant reductions from placebo in hemoglobin A1C, fasting plasma glucose and postprandial glucose in patients with mild to severe type 2 diabetes. In a pooled analysis of the patients treated with 5 mg and 20 mg, the relationship between dose and GLUCOTROL XL's effect of reducing hemoglobin A1C was not established. However, in the case of fasting plasma glucose, patients treated with 20 mg had a statistically significant reduction of fasting plasma glucose compared to the 5 mg-treated group.

The reductions in hemoglobin A1C and fasting plasma glucose were similar in younger and older patients. Efficacy of GLUCOTROL XL was not affected by gender, race or weight (as assessed by body mass index). In long-term extension trials, efficacy of GLUCOTROL XL was maintained in 81% of patients for up to 12 months.

In an open, two-way crossover study, 132 patients were randomly assigned to either GLUCOTROL XL or Glucotrol® for 8 weeks and then crossed over to the other drug for an additional 8 weeks. GLUCOTROL XL administration resulted in significantly lower fasting plasma glucose levels and equivalent hemoglobin A1C levels, as compared to Glucotrol.

In 12 week, well-controlled studies, there was a maximal average net reduction in hemoglobin A1C of 1.7% in absolute units between placebo-treated and GLUCOTROL XL-treated patients.

Other Effects
It has been shown that GLUCOTROL XL therapy is effective in controlling blood glucose without deleterious changes in the plasma lipoprotein profiles of patients treated for type 2 diabetes.

In a placebo-controlled, crossover study in normal volunteers, glipizide had no antidiuretic activity, and, in fact, led to a slight increase in free water clearance.

Pharmacokinetics and Metabolism
Glipizide is rapidly and completely absorbed following oral administration in an immediate release dosage form. The absolute bioavailability of glipizide was 100% after single oral doses in patients with type 2 diabetes. Beginning 2 to 3 hours after administration of GLUCOTROL XL Extended Release Tablets, plasma drug concentrations gradually rise reaching maximum concentrations within 6 to 12 hours after dosing. With subsequent once daily dosing of GLUCOTROL XL Extended Release Tablets, effective plasma glipizide concentrations are maintained throughout the 24 hour dosing interval with less peak to trough fluctuation than that observed with twice daily dosing of immediate release glipizide. The mean relative bioavailability of glipizide in 21 males with type 2 diabetes after administration of 20 mg GLUCOTROL XL Extended Release Tablets, comp