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AM administration of glipizide XR reduces risks of hyperinsulinemia, including increased adiposity and weight gain. Glipizide gastrointestinal therapeutic system (GITS) AM, glipizide GITS PM, and glibenclamide appear to improve fasting plasma glucose and glycosylated hemoglobin [HbA1c] and suppress hepatic glucose production (HGP); however, glipizide GITS AM does so without persistently elevating insulin levels.
Previous studies have established the efficacy and safety of glipizide GITS, a once-daily, extended release formulation of glipizide, but the potential effect of this agent on HGP has not been fully determined.
Eugene H. Go, MD, with Midwestern Endocrinology, in Overland Park, Kansas, United States and colleagues evaluated the effects of glipizide GITS administered once daily (AM or PM) and glibenclamide on glycemic control, insulin secretory response, and HGP in 42 patients with type 2 diabetes and HbA1c between 8.6% and 10.0%.
Eleven participants were randomized to receive a titrated daily dose (5-20 mg) of glipizide GITS AM, 10 to glipizide GITS PM, 11 to glibenclamide, and 10 to placebo.
Glipizide GITS AM significantly reduced fasting and 24-hour glucose (33%, P < .001; 39%, P < .0001), as did glipizide GITS PM (33%, P < .0001; 32%, P < .0001), and glibenclamide (37%, P < .05; 37%, P < .0001). In addition, none of the treatments significantly increased fasting insulin while all 3 treatments significantly reduced fructosamine and HbA1c and decreased the glucose excursion after Sustacal challenge.
Glipizide GITS AM and glibenclamide significantly reduced HGP by approximately 19% (P < .05) and 17% (P < .01), respectively. However, glipizide GITS AM did not significantly increase 24-hour insulin. In contrast, glipizide GITS PM (39%, P < .05) and glibenclamide (23%, P < .05) did significantly increase 24-hour insulin.
According to the researchers, none of the treatments significantly increased body weight and each exhibited a modest beneficial effect on plasma lipids.
"In view of the potential risks associated with chronic hyperinsulinemia, including increased adiposity and weight gain, morning administration of glipizide GITS appears to offer a beneficial approach to reduce these risks," they conclude. Diabetes Metab Res Rev 2004;20:225-231.