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Clinical Pharmacology
CLINICAL PHARMACOLOGY
Mechanism of Action Glipizide appears to lower blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects also may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Text Continues Below
Two extrapancreatic effects shown to be important in the action of glipizide are an increase in insulin sensitivity and a decrease in hepatic glucose production. However, the mechanism by which glipizide lowers blood glucose during long-term administration has not been clearly established. Stimulation of insulin secre-tion by glipizide in response to a meal is of major importance. The insulinotropic response to a meal is enhanced with GLUCOTROL XL administration in diabetic patients. The postprandial insulin and C-peptide responses continue to be enhanced after at least 6 months of treatment. In 2 randomized, double-blind, dose-response studies comprising a total of 347 patients, there was no significant increase in fasting insulin in all GLUCOTROL XL-treated patients combined compared to placebo, although minor elevations were observed at some doses. There was no increase in fasting insulin over the long term. 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 evaluated in 4 therapeutic clinical trials each with long-term open extensions involving a total of 598 patients. Once daily admin-istration of 5, 10 and 20 mg produced statistically significant reductions from placebo in hemoglobin A1C, fasting plasma glu-cose and postprandial glucose in patients with mild to severe type 2 diabetes. Page: 1 | 2 | 3 | 4 | 5 | Next >>
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