Comparative Efficacy of a Once-Daily Controlled-Release Formulation of Glipizide and Immediate-Release Glipizide in Patients With NIDDM
- Michael Berelowitz, MD,
- Christine Fischette, PHD,
- William Cefalu, MD,
- David S Schade, MD,
- Tamara Sutfin, PHD and
- Ione A Kourides, MD
- Division of Endocrinology and Metabolism, SUNY at Stony Brook, Stony Brook, New York; Bowman Gray School of Medicine, Winston-Salem, North Carolina; University of New Mexico School of Medicine Albuquerque, New Mexico; and Pfizer, New York, New York
- Address correspondence and reprint requests to Michael Berelowitz, MD, Division of Endocrinology and Metabolism, HSC 15th Floor, Room 060, SUNY at Stony Brook, Stony Brook, NY 11794.
Abstract
OBJECTIVE To compare the efficacy and safety of controlled-release glipizide (glipizide-GITS [gastrointestinal therapeutic system]) and immediate-release glipizide in patients with non-insulin-dependent diabetes mellitus (NIDDM).
RESEARCH DESIGN AND METHODS In a multicenter, open-label, randomized, two-way crossover study, 132 patients with NIDDM received daily doses of 5, 20, or 40 mg of either glipizide-GITS or immediate-release glipizide for 8 weeks followed by 8 weeks of the alternate formulation. Plasma glucose, serum insulin, C-peptide, and plasma glipizide levels were measured at fasting and post-Sustacal challenge at the end of 1 and 8 weeks of each treatment phase. HbA1c was measured at the end of weeks 7 and 8 of each treatment phase.
RESULTS Both formulations of glipizide yielded similar mean HbA1c values. However, mean fasting plasma glucose (FPG) levels were significantly lower with glipizide-GITS treatment than with immediate-release glipizide at the end of week 1 (11.0 vs. 11.6 mmol/l; P < 0.01) and at the end of the 8-week treatment phase (10.9 vs. 11.7 mmol/l; P < 0.001). Fasting insulin and C-peptide levels were lower after 5 mg glipizide-GITS vs. immediate-release glipizide. Glucose responses to Sustacal were similar after both formulations of glipizide; however, serum insulin (P < 0.01) and C-peptide responses (P < 0.05) were lower with glipizide-GITS than with immediate-release glipizide treatment at the end of the 8-week treatment phase. Mean plasma glipizide concentrations were stable by the end of week 1, and the concentrations increased proportionately with dose. Once-daily Glipizide-GITS provided effective mean glipizide concentrations (> 50 ng/ml) 24 h after dosing, even at the lowest (5 mg) dose level. Both formulations were well tolerated.
CONCLUSIONS Glipizide-GITS was significantly more effective than immediate-release glipizide in reducing FPG levels. Both formulations reduced postprandial plasma glucose levels equally; however, glipizide-GITS exerted its control in the presence of lower plasma glipizide concentrations in addition to significantly lower insulin and C-peptide levels. This suggests that glipizide-GITS improves insulin sensitivity.
- Received April 4, 1994.
- Revision received July 7, 1994.
- Accepted July 7, 1994.
- Copyright © 1994 by the American Diabetes Association
