Effects of glipizide GITS and glibenclamide on metabolic control, hepatic glucose production, and insulin secretion in patients with type 2 diabetes.
OBJECTIVE
Evaluation of effects of glipizide gastrointestinal therapeutic system (GITS) administered once daily (AM or PM) and glibenclamide on glycemic control, insulin secretory response, and hepatic glucose production (HGP) in patients with type 2 diabetes.


METHODS
In a randomized, double-blind, and placebo-controlled study, subjects (HbA(1c) between 8.6 and 10.0%) received a titrated daily dose (5-20 mg) of either glipizide GITS AM (n = 11), glipizide GITS PM (n = 10), glibenclamide (n = 11), or placebo (n = 10) for eight weeks. Fasting and 24-h glucose and insulin, HGP, fructosamine, and HbA(1c) were measured at baseline and at study conclusion; glucose and insulin were also evaluated after Sustacal challenge.


RESULTS
Fasting and 24-h glucose were significantly reduced by glipizide GITS AM (33%, p < 0.001; 39%, p < 0.0001), glipizide GITS PM (33%, p < 0.0001; 32%, p < 0.0001), and glibenclamide (37%, p < 0.05; 37%, p < 0.0001). Fasting insulin was not significantly increased by any treatment; 24-h insulin was not increased by glipizide GITS AM, but was elevated by glipizide GITS PM (39%, p < 0.05) and glibenclamide (23%, p < 0.05). Fructosamine and HbA(1c) were significantly reduced by glipizide GITS AM (28%, p < 0.001; 22%, p < 0.0001), glipizide GITS PM (25%, p < 0.005; 24%, p < 0.005), and glibenclamide (17%, p < 0.001; 14%, p < 0.05). Glipizide GITS AM and glibenclamide significantly reduced HGP by approximately 19% (p < 0.05) and 17% (p < 0.01) respectively. Glipizide GITS and glibenclamide significantly (p < 0.0001) decreased the glucose excursion after Sustacal challenge. The reductions in glucose excursions were accompanied by significant (p < 0.05) increases in the insulin response, suggesting an improvement in meal-related insulin secretion.


CONCLUSIONS
Glipizide GITS and glibenclamide treatment are effective agents for improving fasting plasma glucose and HbA(1c). Each possessed a suppressive effect on basal HGP and improved postprandial glycemia, but only glipizide GITS AM was effective without causing a persistent elevation in insulin. This profile of glipizide GITS AM is therapeutically attractive, as it is consistent with the potential for a reduced risk of hypoglycemia.
Go
Eugene H
EH
Midwestern Endocrinology, PA, USA. goendoc@yahoo.com
Kyriakidou-Himonas
Marinella
M
Berelowitz
Michael
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D019270:Fructosamine / Q000097:blood; D005913:Glipizide / Q000008:administration & dosage*; D005947:Glucose / Q000096:biosynthesis*; D005905:Glyburide / Q000008:administration & dosage*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010919:Placebos
D001786:Blood Glucose; D019270:Fructosamine; D005913:Glipizide; D005947:Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007328:Insulin; D010919:Placebos