Comparative efficacy of a once-daily controlled-release formulation of glipizide and immediate-release glipizide in patients with NIDDM.

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.

• Authors: M Berelowitz, C Fischette, W Cefalu, D S Schade, T Sutfin, I A Kourides
• Journal: Diabetes care (Diabetes Care) Vol. 17 Issue 12 Pg. 1460-4 (Dec 1994) ISSN: 0149-5992 [Print] United States
• PMID: 7882817 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• C-Peptide
• Delayed-Action Preparations
• Glycated Hemoglobin A
• Insulin
• Glipizide

Topics

• Administration, Oral
• Adult
• Aged
• Blood Glucose (metabolism)
• C-Peptide (blood)
• Cross-Over Studies
• Delayed-Action Preparations
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Female
• Glipizide (administration & dosage, blood, therapeutic use)
• Glycated Hemoglobin (analysis)
• Humans
• Insulin (blood)
• Male
• Middle Aged
• Radioimmunoassay